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Virginia Tech
1.
Nealon, Lily Irene.
The Effects of a 5-Day High-Fat Diet on Skeletal Muscle O-GlcNAcylation.
Degree: MS, Human Nutrition, Foods, and Exercise, 2016, Virginia Tech
URL: http://hdl.handle.net/10919/71745 
► Continual intake of high-fat foods, coupled with limited physical activity, can lead to metabolic inflexibility. Eventually, this may lead to significant health issues such as…
(more)
▼ Continual intake of high-fat foods, coupled with limited physical activity, can lead to metabolic inflexibility. Eventually, this may lead to significant health issues such as obesity, insulin resistance, cardiovascular disease, and other chronic diseases. Metabolic flexibility of human skeletal muscles is influenced by changes to mitochondrial, nuclear, and cytosolic proteins, in part as a result of posttranslational modifications (PTMs). O-linked B-D-N-acetylglucosamine, known as O-GlcNAc, has recently been identified as an important posttranslational modification that responds to nutrient sensing and cellular stress. Unlike other PTMs, O-GlcNAc has only two cycling enzymes. Because of its novelty, little research has been performed on the role of O-GlcNAc in human skeletal muscle and metabolic flexibility. The purpose of the current study was to establish the effects of a 5-day high-fat diet on skeletal muscle O-GlcNAcylation. In the proposed study, 13 non-obese, sedentary, college-aged males consumed a controlled diet for two weeks followed by a high-fat diet composed of 55% fat, 30% carbohydrate, and 15% protein. Muscle biopsies were taken from the vastus lateralis both fasted and four hours after a high-fat meal, following both the control diet and the high-fat diet. Western blot analysis was used to assess global O-GlcNAc and protein concentrations of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in whole-homogenates and isolated mitochondria from skeletal muscle. Results were analyzed using independent, two-tailed t-tests and 2-way ANOVA analysis with repeated measures and Bonferroni corrections; a p-value was set to α less than or equal to 0.05. It was found that O-GlcNAc and OGT levels remained stable, although fasting levels of OGA significantly decreased after the 5-day high-fat diet. It is possible that healthy individuals are capable of maintaining normal levels of O-GlcNAc and its cycling enzymes, but there is still more to learn about O-GlcNAc and its role in metabolic flexibility.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Frisard, Madlyn I. (committee member), Neilson, Andrew P. (committee member).
Subjects/Keywords: O-GlcNAc; skeletal muscle metabolism; nutrition; physiology
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APA (6th Edition):
Nealon, L. I. (2016). The Effects of a 5-Day High-Fat Diet on Skeletal Muscle O-GlcNAcylation. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/71745
Chicago Manual of Style (16th Edition):
Nealon, Lily Irene. “The Effects of a 5-Day High-Fat Diet on Skeletal Muscle O-GlcNAcylation.” 2016. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/71745.
MLA Handbook (7th Edition):
Nealon, Lily Irene. “The Effects of a 5-Day High-Fat Diet on Skeletal Muscle O-GlcNAcylation.” 2016. Web. 16 Jan 2021.
Vancouver:
Nealon LI. The Effects of a 5-Day High-Fat Diet on Skeletal Muscle O-GlcNAcylation. [Internet] [Masters thesis]. Virginia Tech; 2016. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/71745.
Council of Science Editors:
Nealon LI. The Effects of a 5-Day High-Fat Diet on Skeletal Muscle O-GlcNAcylation. [Masters Thesis]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/71745
2.
Lupi, Ryan Alexander.
Regulation of human satellite cells in vitro via inflammatory cytokines and myogenic transcription factors across proliferation and differentiation.
Degree: MS, Human Nutrition, Foods, and Exercise, 2019, Virginia Tech
URL: http://hdl.handle.net/10919/90390
► Skeletal muscle is responsible for conscious, voluntary movement. In addition, the tissue is responsible for the majority of energy expenditure in the human body. Skeletal…
(more)
▼ Skeletal muscle is responsible for conscious, voluntary movement. In addition, the tissue is responsible for the majority of energy expenditure in the human body. Skeletal muscle is able to adapt to exercise programs through the fusion of undifferentiated stem cells – called satellite cells – in the skeletal muscle fiber. In long-term diseased conditions, the immune response involves chronic rises in inflammation and results in the loss of skeletal muscle and corresponding loss of ability to move. A shorter rise in inflammation is also linked with the positive exercise response. Our study features satellite cells harvested from muscle samples of 12 male human research participants. We were interested in evaluating the relationships between the expression and secretion of two proteins associated with inflammation and regulation of the satellite cell cycle. The two proteins of interest in our study are tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). We also measure the gene expression of another inflammatory protein, transforming growth factor beta (TGF-β). In order to know where the cells were in their life cycle, we measured expression of genes associated with the division (Pax7), early fusion (MyoD), and late fusion of satellite cells (myogenin). Our study found a decrease in IL-6 secretion and expression as the process of satellite cells turning into muscle fibers was initiated. Additionally, a 50-fold increase in IL-6 expression was found at day 7 compared to day 0 of the satellite cell cycle. Additionally, we found a positive correlation between TGF-β and myogenin and a negative correlation between IL-6 and MyoD. Although we found correlations between satellite cell cycle genes and inflammation genes, more research is necessary to see if there is a pathway causing this relationship.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Gilbert, Elizabeth R. (committee member), Good, Deborah J. (committee member).
Subjects/Keywords: skeletal muscle; humans; satellite cells; inflammation; inflammatory cytokine; exercise; endurance training
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APA (6th Edition):
Lupi, R. A. (2019). Regulation of human satellite cells in vitro via inflammatory cytokines and myogenic transcription factors across proliferation and differentiation. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/90390
Chicago Manual of Style (16th Edition):
Lupi, Ryan Alexander. “Regulation of human satellite cells in vitro via inflammatory cytokines and myogenic transcription factors across proliferation and differentiation.” 2019. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/90390.
MLA Handbook (7th Edition):
Lupi, Ryan Alexander. “Regulation of human satellite cells in vitro via inflammatory cytokines and myogenic transcription factors across proliferation and differentiation.” 2019. Web. 16 Jan 2021.
Vancouver:
Lupi RA. Regulation of human satellite cells in vitro via inflammatory cytokines and myogenic transcription factors across proliferation and differentiation. [Internet] [Masters thesis]. Virginia Tech; 2019. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/90390.
Council of Science Editors:
Lupi RA. Regulation of human satellite cells in vitro via inflammatory cytokines and myogenic transcription factors across proliferation and differentiation. [Masters Thesis]. Virginia Tech; 2019. Available from: http://hdl.handle.net/10919/90390
Virginia Tech
3.
Zhang, Shuai.
Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue.
Degree: MS, Animal and Poultry Sciences, 2013, Virginia Tech
URL: http://hdl.handle.net/10919/24536
► The ability to adapt fuel usage to nutrient availability is termed metabolic flexibility, and is influenced by activity of the pyruvate dehydrogenase complex (PDC). The…
(more)
▼ The ability to adapt fuel usage to nutrient availability is termed metabolic flexibility, and is influenced by activity of the pyruvate dehydrogenase complex (PDC). The
Virginia lines of chickens are a unique model of anorexia and obesity that have resulted from 56 generations of artificial selection for high (HWS) or low (LWS) juvenile body weight. We hypothesized that hyperphagia and obesity in juvenile HWS chickens are associated with altered fatty acid oxidation efficiency and metabolic flexibility in tissues associated with energy sensing and storage, and relative cellular hypertrophy in white adipose tissue. Hypothalamus, liver, Pectoralis major, gastrocnemius, abdominal fat, clavicular fat and subcutaneous fat were collected from juvenile (56-65 day-old) HWS and LWS chickens for metabolic, gene expression and histological assays. The HWS chickens had reduced fatty acid oxidation efficiency in abdominal fat (P < 0.0001) and reduced rates of oxidation in abdominal fat and gastrocnemius (P < 0.0001) as compared to LWS. There was reduced citrate synthase activity in white adipose tissue (P < 0.0001) and greater metabolic inflexibility in skeletal muscle (P = 0.006) of HWS compared to LWS. Greater pyruvate dehydrogenase kinase 4 (PDK4) and forkhead box O1 (FoxO1) mRNA were found in skeletal muscle and white adipose tissue of 56-day-old HWS than LWS. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in all adipose tissue depots was greater (P < 0.05) in LWS than in HWS chickens. The HWS chickens had larger (P < 0.0001) and fewer (P < 0.0001) adipocytes per unit area than LWS. These results suggest that the HWS chickens have impaired metabolic flexibility and fatty acid oxidation efficiency due to an up-regulation of pyruvate dehydrogenase activity to accommodate the influx of acetyl CoA from fatty acid oxidation in skeletal muscle and white adipose tissue. These metabolic adaptations can be linked to differences in gene expression regulation and body composition between the lines. Adipocyte cellularity data are consistent with greater oxidative efficiency in the adipose tissue of LWS, because of the greater number of unfilled cells in all depots that were sampled. Results can be extrapolated to agricultural production in the understanding of factors regulating the amount of lipid deposition in chicken carcass fat. Results may also provide insight into eating disorders and the development of obesity.
Advisors/Committee Members: Gilbert, Elizabeth R. (committeechair), Cline, Mark Andrew (committee member), Siegel, Paul B. (committee member), Hulver, Matthew W. (committee member).
Subjects/Keywords: fatty acid oxidation; metabolic flexibility; PDH; PDK4; FoxO1; PPARγ
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APA (6th Edition):
Zhang, S. (2013). Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/24536
Chicago Manual of Style (16th Edition):
Zhang, Shuai. “Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue.” 2013. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/24536.
MLA Handbook (7th Edition):
Zhang, Shuai. “Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue.” 2013. Web. 16 Jan 2021.
Vancouver:
Zhang S. Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue. [Internet] [Masters thesis]. Virginia Tech; 2013. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/24536.
Council of Science Editors:
Zhang S. Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue. [Masters Thesis]. Virginia Tech; 2013. Available from: http://hdl.handle.net/10919/24536
Virginia Tech
4.
Shea, Amanda Ann.
The Impact of Adipose-Associated Stromal Cells on the Metastatic Potential of Ovarian Cancer.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2014, Virginia Tech
URL: http://hdl.handle.net/10919/54562
► Obesity is a major global health concern due to its steadily increasing rates and significant contribution to numerous diseases, including cancer. Ovarian cancer specifically, is…
(more)
▼ Obesity is a major global health concern due to its steadily increasing rates and significant contribution to numerous diseases, including cancer. Ovarian cancer specifically, is associated with a 30% increased risk with obesity, although the mechanisms for this are unknown. Waist-to-hip ratio has been especially associated with ovarian cancer, suggesting that visceral fat may be the greatest
contributor. Here, we investigated individual visceral fat depots as independent contributors to cancer progression, specifically focusing on adipose tissue-derived stem and progenitor cells, which have previously been shown to be recruited by cancer cells and participate in cancer progression. We confirmed that ovarian cancer tumor burden was indeed significantly increased in mice on a high fat as compared to low fat diet. To further investigate mechanisms, we examined changes in progenitor populations that occurred in intra-abdominal parametrial (pmWAT), retroperitoneal (rpWAT), and omental (omWAT) white adipose tissue (WAT) depots with cancer presence. The greatest tumor burden was evident in omWAT, which also displayed an increase in CD45- cells but a decrease in adipose progenitor cells (APC) and endothelial progenitor cells, suggesting that there was an increase in stromal cells, but that the stem cells were pushed towards differentiation. PmWAT and rpWAT showed remarkably stable progenitor populations. However, a tumor from pmWAT had a significant presence of CD45- cells, actually matching that of its surrounding tissue and differing from the omWAT tumors, indicating that microenvironment has a major influence on tumor stromal cells. We also found that with high fat diet, many cancer-associated changes were exacerbated, such as an increased inflammatory response in all tissues and further decreases in APCs in omWAT. In vitro studies further confirmed that ovarian cancer cells and SVF cells were able to directly interact. Additionally, SVF cells were able to increase the proliferation, mobility, and invasiveness of cancer cells. Conversely, co-culturing also enhanced the proliferation and mobility of SVF cells, providing further evidence that SVF cells may be recruited by cancer cells and that their relationship may be bilateral. Thus, this study provides a good foundation for examining the cellular contributions of adipose tissue to cancer. By further characterizing the mechanism for the association between obesity and cancer development, we could find novel targets to decrease the progress of cancer development in at-risk obese individuals.
Advisors/Committee Members: Schmelz, Eva Maria (committeechair), Roberts, Paul Christopher (committee member), Hulver, Matthew W. (committee member), Frisard, Madlyn I. (committee member).
Subjects/Keywords: ovarian cancer; obesity; adipose tissue; progenitor cells
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APA (6th Edition):
Shea, A. A. (2014). The Impact of Adipose-Associated Stromal Cells on the Metastatic Potential of Ovarian Cancer. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/54562
Chicago Manual of Style (16th Edition):
Shea, Amanda Ann. “The Impact of Adipose-Associated Stromal Cells on the Metastatic Potential of Ovarian Cancer.” 2014. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/54562.
MLA Handbook (7th Edition):
Shea, Amanda Ann. “The Impact of Adipose-Associated Stromal Cells on the Metastatic Potential of Ovarian Cancer.” 2014. Web. 16 Jan 2021.
Vancouver:
Shea AA. The Impact of Adipose-Associated Stromal Cells on the Metastatic Potential of Ovarian Cancer. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/54562.
Council of Science Editors:
Shea AA. The Impact of Adipose-Associated Stromal Cells on the Metastatic Potential of Ovarian Cancer. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/54562
Virginia Tech
5.
Wahlberg, Kristin.
The Role of Angiotensin II in Skeletal Muscle Metabolism.
Degree: MS, Human Nutrition, Foods, and Exercise, 2011, Virginia Tech
URL: http://hdl.handle.net/10919/42504
► Hypertension and diabetes have long been closely linked. As such, the major player in the renin, angiotensin system, angiotensin II, has recently been investigated for…
(more)
▼ Hypertension and diabetes have long been closely linked. As such, the major player in the renin, angiotensin system, angiotensin II, has recently been investigated for its effects on metabolism and diabetes. Since skeletal muscle is one of the most metabolically active tissues, this study investigates the effects of angiotensin II specifically on skeletal muscle. In this study, L6 skeletal muscle cells were treated with angiotensin II for either 3 or 24 hours and a number of effects were investigated. Fatty acid oxidation and lipid synthesis was measured using [1-14C]-palmitate, glucose oxidation and glycogen synthesis were measured using 14C-glucose. In addition,mitochondrial oxidative capacity was measured using an XF 24 Flux Analyzer (Seahorse Bioscience) and reactive oxygen species measured using confocal microscopy. The clinical study involving the drug Benicar ® investigated the metabolic effects of blocking angiotensin II on skeletal muscle fatty acid oxidation, glucose oxidation, and oxidative and glycolytic enzyme activity. In L6 cells, angiotensin II significantly reduced fatty acid oxidation after 24 hours (p<0.01) and 3 hours (p<0.001) if angiotensin II was present during oxidation experiments. It also significantly reduced mitochondrial oxidative capacity (p<0.05) after 24 hours and significantly increased reactive oxygen species production (p<0.05) over 3 hours. The clinical study showed no significant effects of Benicar® on fatty acid or glucose oxidation or any enzyme activities.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Li, Liwu (committee member), Frisard, Madlyn I. (committee member), Davy, Kevin P. (committee member).
Subjects/Keywords: ROS; oxidation; skeletal muscle; angiotensin II
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APA (6th Edition):
Wahlberg, K. (2011). The Role of Angiotensin II in Skeletal Muscle Metabolism. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/42504
Chicago Manual of Style (16th Edition):
Wahlberg, Kristin. “The Role of Angiotensin II in Skeletal Muscle Metabolism.” 2011. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/42504.
MLA Handbook (7th Edition):
Wahlberg, Kristin. “The Role of Angiotensin II in Skeletal Muscle Metabolism.” 2011. Web. 16 Jan 2021.
Vancouver:
Wahlberg K. The Role of Angiotensin II in Skeletal Muscle Metabolism. [Internet] [Masters thesis]. Virginia Tech; 2011. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/42504.
Council of Science Editors:
Wahlberg K. The Role of Angiotensin II in Skeletal Muscle Metabolism. [Masters Thesis]. Virginia Tech; 2011. Available from: http://hdl.handle.net/10919/42504
6.
Rockwell, Michelle S.
Vitamin D in Human Health and Performance: The Pursuit of Evidence-Based Practice in an Era of Scientific Uncertainty.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2019, Virginia Tech
URL: http://hdl.handle.net/10919/93168
► Vitamin D is known as the “sunshine vitamin” since it can be synthesized by the human body when exposed to specific wavelengths of ultraviolet-B (UVB)…
(more)
▼ Vitamin D is known as the “sunshine vitamin” since it can be synthesized by the human body when exposed to specific wavelengths of ultraviolet-B (UVB) light. Some foods and dietary supplements also contain vitamin D. A relationship between vitamin D and bone health is well-established, but emerging research has also associated vitamin D status with a number of different diseases and health problems, including cancer, cardiovascular disease, autoimmune conditions, and depression. Unfortunately, this research is currently inconclusive, and healthcare providers’ professional guidelines related to vitamin D are highly variable. Thus, providing evidence-based care related to vitamin D is complicated. This dissertation consists of a series of three research studies that describe healthcare providers’ vitamin D-related care considering the uncertain landscape, and two research studies that explore the role of vitamin D in collegiate athletes. We chose athletes since a high proportion of them have deficient or insufficient vitamin D status, and because some research has shown that this low vitamin D status affects athletic performance. Results of these studies showed that vitamin D-related health services such as blood testing have increased dramatically over the past 15 years, as have costs associated with these services. Opportunities to improve consistency and quality of care were observed in multiple settings. In the athlete studies, a high rate of vitamin D deficiency and insufficiency was observed among basketball athletes, and we identified vitamin D supplement treatment protocol effective in improving vitamin D status. In addition, swimmers who took vitamin D supplements performed better on strength and conditioning tests than those who took placebo supplements. A favorable relationship between testosterone concentrations and vitamin D status was shown in both basketball athletes and swimmers. Continuing to conduct research focused on specific populations can help healthcare providers develop consistent, high quality, evidence-based care related to vitamin D.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Davy, Kevin P. (committee member), Epling, John (committee member), Rankin, Janet L. Walberg (committee member), You, Wen (committee member).
Subjects/Keywords: Low Value Care; Screening; 25-Hydroxyvitamin D; Supplement; Athlete
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APA (6th Edition):
Rockwell, M. S. (2019). Vitamin D in Human Health and Performance: The Pursuit of Evidence-Based Practice in an Era of Scientific Uncertainty. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/93168
Chicago Manual of Style (16th Edition):
Rockwell, Michelle S. “Vitamin D in Human Health and Performance: The Pursuit of Evidence-Based Practice in an Era of Scientific Uncertainty.” 2019. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/93168.
MLA Handbook (7th Edition):
Rockwell, Michelle S. “Vitamin D in Human Health and Performance: The Pursuit of Evidence-Based Practice in an Era of Scientific Uncertainty.” 2019. Web. 16 Jan 2021.
Vancouver:
Rockwell MS. Vitamin D in Human Health and Performance: The Pursuit of Evidence-Based Practice in an Era of Scientific Uncertainty. [Internet] [Doctoral dissertation]. Virginia Tech; 2019. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/93168.
Council of Science Editors:
Rockwell MS. Vitamin D in Human Health and Performance: The Pursuit of Evidence-Based Practice in an Era of Scientific Uncertainty. [Doctoral Dissertation]. Virginia Tech; 2019. Available from: http://hdl.handle.net/10919/93168
Virginia Tech
7.
Al-Rayyan, Numan A.
Transcriptional and Post-transcriptional Control of Nhlh2 with Differing Energy Status.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2011, Virginia Tech
URL: http://hdl.handle.net/10919/77123
► Nescient Helix Loop Helix 2 (Nhlh2) is a member of the basic helix-loop-helix transcription factor family. Mice with a targeted deletion of Nhlh2, called N2KO…
(more)
▼ Nescient Helix Loop Helix 2 (Nhlh2) is a member of the basic helix-loop-helix transcription factor family. Mice with a targeted deletion of Nhlh2, called N2KO mice, show adult onset obesity in both males and females. Nhlh2 regulates other genes by binding to the E-box in the promoter region of these genes. This transcription factor regulates many other transcription factors including MC4R and PC1/3 which are associated with human obesity. The Nhlh2 promoter has been analyzed for putative transcription factors binding sites. These putative binding sites have been tested to be the regulators of Nhlh2 by transactivation assays with mutant promoters, Electrophoretic Shift Assay (EMSA), and Chromatin Immunoprecipitation Assay (ChIP) as methods to investigate the DNA-protein binding.
The results of these experiments showed that the Nhlh2 promoter has five Signal Transducer and Activator of Transcription 3 (Stat3) binding site motifs at -47, -65, -80, -281, -294 and two Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NFκB) binding site motifs at -67 and -135. While NFκB acts as a negative regulator of Nhlh2, this research showed that Stat3 acts as a regulator for the Nhlh2 basal expression and leptin stimulation. The ChIP assay using chromatin from mouse hypothalamus and antibodies against Stat3 and the NFκB subunits P50, P65, and c-Rel demonstrated that all of these antibodies were able to pull down the part of the Nhlh2 promoter containing the binding sites of Stat3 and NFκB. The EMSA results not only demonstrated that NFκB and Stat3 binding site motifs are real binding sites, but also exists the possibility of a relationship between these transcription factors to regulate Nhlh2 expression with leptin stimulation.
An effort in analyzing the human NHLH2 3'UTR showed that one of the SNPs located at position 1568 in the NHLH2 mRNA (NHLH2A
1568G) which converts adenosine to guanine might have the potential to decrease the mRNA stability. For more investigation about this SNP, the mouse Nhlh2 tail was cloned into 2 different vectors and these vectors were subjected to site directed mutagenesis to create the 3'UTR SNP that convert A to G. One of these vectors used luciferase as a reporter gene for expression while the other one was used to measure Nhlh2 mRNA stability. These vectors were transfected into hypothalamic cell line N29/2 to test the effect of this SNP on Nhlh2 expression. This study demonstrated that this SNP down regulated luciferase expression and also decreased Nhlh2 mRNA stability.
Taken together, this study demonstrated that Nhlh2 could be regulated transcriptionally by both NFκB and Stat3 transcription factors and post-transcripitionally by the 3'UTR SNP that converts adenosine to guanine.
Advisors/Committee Members: Good, Deborah J. (committeechair), Tu, Zhijian Jake (committee member), Hulver, Matthew W. (committee member), Wong, Eric A. (committee member).
Subjects/Keywords: NFκB; Stat3; mRNA stability; 3'UTR; SNP; Obesity; Nhlh2; Energy expenditure; Transcription
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APA (6th Edition):
Al-Rayyan, N. A. (2011). Transcriptional and Post-transcriptional Control of Nhlh2 with Differing Energy Status. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/77123
Chicago Manual of Style (16th Edition):
Al-Rayyan, Numan A. “Transcriptional and Post-transcriptional Control of Nhlh2 with Differing Energy Status.” 2011. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/77123.
MLA Handbook (7th Edition):
Al-Rayyan, Numan A. “Transcriptional and Post-transcriptional Control of Nhlh2 with Differing Energy Status.” 2011. Web. 16 Jan 2021.
Vancouver:
Al-Rayyan NA. Transcriptional and Post-transcriptional Control of Nhlh2 with Differing Energy Status. [Internet] [Doctoral dissertation]. Virginia Tech; 2011. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/77123.
Council of Science Editors:
Al-Rayyan NA. Transcriptional and Post-transcriptional Control of Nhlh2 with Differing Energy Status. [Doctoral Dissertation]. Virginia Tech; 2011. Available from: http://hdl.handle.net/10919/77123
Virginia Tech
8.
Donnelly, Sarah Rebecca.
Temporal examination of DNA methylation profile reprogramming in the promoter region of PGC-1α during the progression of insulin resistance and type 2 diabetes mellitus in rodent models.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2019, Virginia Tech
URL: http://hdl.handle.net/10919/92592
► High blood glucose, referred to as type 2 diabetes (T2DM), increases the risk for heart and kidney disease, blindness, stroke, and death. Efforts to prevent…
(more)
▼ High blood glucose, referred to as type 2 diabetes (T2DM), increases the risk for heart and kidney disease, blindness, stroke, and death. Efforts to prevent T2DM have centered primarily around behavioral interventions, which include increased physical activity and decreased caloric intake. Importantly, the interventions are most effective when implemented early on in disease progression. In this study, we sought to examine the effects of a high fat diet on the epigenetic profile of PGC-1α, a gene responsible for maintaining mitochondrial biogenesis. The mitochondria, the powerhouse of the cell, is responsible for maintaining the energy systems in the body. Therefore, we examined how increasing in caloric intake resulted in changes in the epigenetic profile of the PGC-1α promoter, and how these changes impacted mitochondrial number. Further, we sought to examine how hypermethylation of PGC-1α led to changes in gene and protein expression in the mitochondria. Results from our study indicate that DNA methylation changes preceded disease onset, as characterized by the homeostatic model assessment for insulin resistance (HOMA-IR), the homeostatic model assessment for β-cell dysfunction (HOMA- β), and the quantitative insulin-sensitivity check index (QUICKI). Our data indicate that methylation analysis may serve as diagnostic and risk assessment tool for pre-diabetes and T2DM in conjunction with physiological measures.
Advisors/Committee Members: Cheng, Zhiyong (committeechair), Schmelz, Eva M. (committeechair), Hulver, Matthew W. (committee member), Almeida, Fabio A. (committee member), McMillan, Ryan P. (committee member).
Subjects/Keywords: type 2 diabetes mellitus; epigenetics; mitochondria; methylation
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APA (6th Edition):
Donnelly, S. R. (2019). Temporal examination of DNA methylation profile reprogramming in the promoter region of PGC-1α during the progression of insulin resistance and type 2 diabetes mellitus in rodent models. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/92592
Chicago Manual of Style (16th Edition):
Donnelly, Sarah Rebecca. “Temporal examination of DNA methylation profile reprogramming in the promoter region of PGC-1α during the progression of insulin resistance and type 2 diabetes mellitus in rodent models.” 2019. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/92592.
MLA Handbook (7th Edition):
Donnelly, Sarah Rebecca. “Temporal examination of DNA methylation profile reprogramming in the promoter region of PGC-1α during the progression of insulin resistance and type 2 diabetes mellitus in rodent models.” 2019. Web. 16 Jan 2021.
Vancouver:
Donnelly SR. Temporal examination of DNA methylation profile reprogramming in the promoter region of PGC-1α during the progression of insulin resistance and type 2 diabetes mellitus in rodent models. [Internet] [Doctoral dissertation]. Virginia Tech; 2019. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/92592.
Council of Science Editors:
Donnelly SR. Temporal examination of DNA methylation profile reprogramming in the promoter region of PGC-1α during the progression of insulin resistance and type 2 diabetes mellitus in rodent models. [Doctoral Dissertation]. Virginia Tech; 2019. Available from: http://hdl.handle.net/10919/92592
Virginia Tech
9.
Scheffler, Tracy Leigh.
AMP-activated protein kinase and muscle metabolism.
Degree: PhD, Animal and Poultry Sciences, 2012, Virginia Tech
URL: http://hdl.handle.net/10919/38829
► AMP-activated protein kinase (AMPK) is a major regulator of skeletal muscle metabolism with relevance to agriculture and human health. During the conversion of muscle to…
(more)
▼ AMP-activated protein kinase (AMPK) is a major regulator of skeletal muscle metabolism with relevance to agriculture and human health. During the conversion of muscle to meat, the rate and extent of postmortem metabolism and pH decline largely determine pork quality development. Pigs with the AMPKγ3 R200Q mutation generate pork with low ultimate pH (pHu); this is attributed to high glycogen content, and greater â potentialâ to produce lactate and H+. We hypothesized that decreasing muscle phosphocreatine and creatine would decrease ATP buffering capacity, resulting in earlier termination of glycolysis and pH decline. Dietary supplementation with the creatine analogue, β-GPA, decreased muscle total creatine but negatively affected performance. Another experiment was conducted using control or β-GPA diet and wild type and AMPKγ3R200Q pigs in a 2à 2 factorial design. The loss of muscle total creatine was important in maintenance of ATP levels in AMPKγ3R200Q muscle early postmortem. Moreover, elevated glycogen did not affect pHu, supporting that energetic modifications induced by feed restriction and β-GPA supplementation influence extent of pH decline. Next, we utilized a line of pigs selected for differences in pHu. Another AMPKγ3 mutation (V199I), which is associated with higher pHu and lower glycolytic potential, was prevalent. The 199II genotype increased pHu in castrated males only. The wild type VV genotype increased glycolytic potential, but neither glycolytic potential nor lactate predicted pHu.
In humans, AMPK activation is at least partly responsible for the beneficial effects of exercise on glucose transport and increased oxidative capacity in skeletal muscle. An inverse relationship exists between skeletal muscle fiber cross-sectional area and oxidative capacity, which suggests muscle fibers hypertrophy at the expense of oxidative capacity. Therefore, we utilized pigs possessing mutations associated with increased oxidative capacity (AMP-activated protein kinase, AMPKγ3R200Q) or fiber hypertrophy (ryanodine receptor 1, RyR1R615C) to determine if these events occur in parallel. RyR1R615C increased muscle fiber size; AMPKγ3R200Q increased oxidative capacity, evidenced by enhanced enzyme activity, mitochondrial function, and expression of mitochondrial proteins. Thus, pigs with both AMPKγ3R200Q and RyR1R615C possess increased fiber size and oxidative capacity, suggesting hypertrophy and oxidative capacity can occur simultaneously in skeletal muscle.
Advisors/Committee Members: Gerrard, David E. (committeechair), Escobar, Jeffery (committee member), Sobrado, Pablo (committee member), Hulver, Matthew W. (committee member), Frisard, Madlyn I. (committee member).
Subjects/Keywords: calcium; mitochondria; pork quality; skeletal muscle
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APA (6th Edition):
Scheffler, T. L. (2012). AMP-activated protein kinase and muscle metabolism. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/38829
Chicago Manual of Style (16th Edition):
Scheffler, Tracy Leigh. “AMP-activated protein kinase and muscle metabolism.” 2012. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/38829.
MLA Handbook (7th Edition):
Scheffler, Tracy Leigh. “AMP-activated protein kinase and muscle metabolism.” 2012. Web. 16 Jan 2021.
Vancouver:
Scheffler TL. AMP-activated protein kinase and muscle metabolism. [Internet] [Doctoral dissertation]. Virginia Tech; 2012. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/38829.
Council of Science Editors:
Scheffler TL. AMP-activated protein kinase and muscle metabolism. [Doctoral Dissertation]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/38829
Virginia Tech
10.
Anderson, Angela S.
Characterization of Metabolic Differences in Benign, Slow Developing and Tumor Initiating Ovarian Cancers.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2013, Virginia Tech
URL: http://hdl.handle.net/10919/50812
► Ovarian cancer is known as the "silent killer," due to its late diagnosis and frequent recurrence after initial treatment. Finding a new way to diagnose…
(more)
▼ Ovarian cancer is known as the "silent killer," due to its late diagnosis and frequent recurrence after initial treatment. Finding a new way to diagnose and treat ovarian cancer in conjunction with current therapies is paramount. By capitalizing on metabolic changes that occur during cancer progression, interventions can be developed. The Nobel laureate Otto Warburg is credited with discovering an altered metabolic state within cancer cells known as the Warburg effect. In the Warburg effect, cancer cells participate in an increased rate of aerobic glycolysis with an excess secretion of lactate, allowing for carbon flux into biosynthetic pathways. Exactly which metabolic pathways are altered in ovarian cancer and at which stage in the progression of ovarian cancer they are occurring was unknown. Therefore using the recently established mouse ovarian surface epithelial (MOSE) progression model, we were able to measure metabolic changes in varying states of disease and levels of aggressiveness. As cells progressed from a benign early stage (MOSE-E), through a transitional intermediate stage (MOSE-I), to an aggressive late stage (MOSE-L), the MOSE cells became more glycolytic and lipogenic, establishing the MOSE model as a valuable model for studying ovarian cancer metabolism. Treating the MOSE cells with the naturally occurring chemotherapeutic agent sphingosine decreased p-AKT protein levels in the cell, decreased the glycolytic rate and decreased de novo cholesterol synthesis. Cancer stem cells are known to be resistant to chemotherapy treatments and targeting their metabolism may be promising for combinatorial treatments. Therefore, the metabolism of highly aggressive tumor-initiating cells (TIC), harvested from ascites of C57Bl/6 mice injected with MOSE-L cells were characterized. Although the basal metabolism of the TICs was similar to the MOSE-L cells, TICs were more resistant to cell death as a consequence of external stresses and substrate depletion. The TICs could also up-regulate oxygen consumption rate (OCR) when uncoupled and increase glycolysis when ATP Synthase was inhibited, highlighting their resiliency. Taken together, we have identified targets for treatment strategies that could suppress the growth of primary tumors and may be effective against TICs, thereby suppressing tumor recurrence and possibly prolonging the life of women with ovarian cancer.
Advisors/Committee Members: Schmelz, Eva M. (committeechair), Hulver, Matthew W. (committeechair), Roberts, Paul C. (committee member), Frisard, Madlyn I. (committee member).
Subjects/Keywords: Ovarian cancer; metabolism; Warburg effect; cancer stem cells; mitochondria
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APA (6th Edition):
Anderson, A. S. (2013). Characterization of Metabolic Differences in Benign, Slow Developing and Tumor Initiating Ovarian Cancers. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/50812
Chicago Manual of Style (16th Edition):
Anderson, Angela S. “Characterization of Metabolic Differences in Benign, Slow Developing and Tumor Initiating Ovarian Cancers.” 2013. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/50812.
MLA Handbook (7th Edition):
Anderson, Angela S. “Characterization of Metabolic Differences in Benign, Slow Developing and Tumor Initiating Ovarian Cancers.” 2013. Web. 16 Jan 2021.
Vancouver:
Anderson AS. Characterization of Metabolic Differences in Benign, Slow Developing and Tumor Initiating Ovarian Cancers. [Internet] [Doctoral dissertation]. Virginia Tech; 2013. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/50812.
Council of Science Editors:
Anderson AS. Characterization of Metabolic Differences in Benign, Slow Developing and Tumor Initiating Ovarian Cancers. [Doctoral Dissertation]. Virginia Tech; 2013. Available from: http://hdl.handle.net/10919/50812
Virginia Tech
11.
Luo, Jing.
Investigating the potential anti-diabetic effect of sulforaphane.
Degree: MS, Human Nutrition, Foods, and Exercise, 2014, Virginia Tech
URL: http://hdl.handle.net/10919/49264
► Type 2 diabetes (T2D) is a major public health issue worldwide and it currently affects nearly 26 million people in the United States. It is…
(more)
▼ Type 2 diabetes (T2D) is a major public health issue worldwide and it currently affects nearly 26 million people in the United States. It is estimated that one third of Americans will have diabetes by 2050. T2D is a result of chronic insulin resistance and loss of beta-cell mass and function. Both in experimental animals and people, obesity is a leading pathogenic factor for developing insulin resistance, which is always associated with the impairment in energy metabolism, causing increased intracellular fat content in skeletal muscle, liver, fat, as well as pancreatic islets. Constant insulin resistance will progress to T2D when beta-cells are unable to secret adequate amount of insulin to compensate for decreased insulin sensitivity. In the present study, I investigated whether sulforaphane, a natural compound derived from cruciferous vegetables, can prevent high-fat (HF) diet-induced obesity and diabetes in C57BL/6 mice. Dietary intake of sulforaphane (250 mg/kg diet) prevented hyperglycemia and increased insulin sensitivity in HF diet-induced obese mice. Mice treated with sulforaphane had significant lower serum insulin levels (1.93±0.11 μg/dl) as compared to those without treatment (3.09±0.27 μg/dl, P<0.05). In second study, administration of sulforaphane (40 mg/kg body weight daily via gavage) in obese mice enhanced body weight loss and improved insulin sensitivity. Moreover, sulforaphane increased pyruvate oxidation by 28.85% (P<0.05) and enhanced fatty acid oxidation efficiency by 2.2 fold (P<0.05) in primary human muscle cells. These results suggest that sulforaphane may be a naturally occurring insulin-sensitizing agent that is capable of preventing T2D.
Advisors/Committee Members: Liu, Dongmin (committeechair), Jiang, Honglin (committee member), Ju, Young Hwa (committee member), Hulver, Matthew W. (committee member).
Subjects/Keywords: Sulforaphane; Obesity; T2D; Insulin Sensitivity
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APA (6th Edition):
Luo, J. (2014). Investigating the potential anti-diabetic effect of sulforaphane. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/49264
Chicago Manual of Style (16th Edition):
Luo, Jing. “Investigating the potential anti-diabetic effect of sulforaphane.” 2014. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/49264.
MLA Handbook (7th Edition):
Luo, Jing. “Investigating the potential anti-diabetic effect of sulforaphane.” 2014. Web. 16 Jan 2021.
Vancouver:
Luo J. Investigating the potential anti-diabetic effect of sulforaphane. [Internet] [Masters thesis]. Virginia Tech; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/49264.
Council of Science Editors:
Luo J. Investigating the potential anti-diabetic effect of sulforaphane. [Masters Thesis]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/49264
Virginia Tech
12.
Ringwood, Lorna Ann.
Role of IRAK-1 in the Dynamic Regulation of Reactive Oxygen Species.
Degree: PhD, Biology, 2011, Virginia Tech
URL: http://hdl.handle.net/10919/77203
► Generation of reactive oxygen species (ROS) by mammalian host cells is a double-edged sword. ROS are clearly beneficial in directly killing pathogens and as a…
(more)
▼ Generation of reactive oxygen species (ROS) by mammalian host cells is a double-edged sword. ROS are clearly beneficial in directly killing pathogens and as a signaling molecule to alert macrophages and neutrophils to the site of infection. However, ROS are also capable of damaging host cells by destroying DNA, oxidizing proteins and lipids, inactivating enzymes, and eliciting apoptosis. Therefore the balance of ROS generation and clearance is essential for homeostasis. Although multiple mechanisms can contribute to the generation of ROS, NADPH oxidase (Nox) is a primary producer. In terms of clearance, several ROS scavenging enzymes are induced by Nrf2, a sensor of excessive ROS. The mechanisms behind the skewing of this balance toward prolonged accumulation of ROS under chronic inflammatory conditions are not well understood.
Lipopolysaccharide (LPS), a major component of the Gram-negative bacteria cell wall, is specifically recognized by Toll-like receptor 4 (TLR4). LPS triggers robust activation of Nox and ROS production through TLR4, while also activating Nrf2 and ROS clearance. Intracellular pathways regulating ROS generation and clearance mediated by TLR4 are not well defined. Since interleukin-1 receptor associated kinase 1 (IRAK-1) is a key downstream component of TLR4, we test the hypothesis that IRAK-1 may play a critical role in maintaining the balance of LPS triggered ROS generation and clearance.
Using wild type and IRAK-1 deficient murine embryonic fibroblasts, we tested the dynamic induction of Nox1 (a key NADPH oxidase) and Nrf2 by varying dosages of LPS. Our data confirm that high dose LPS (as seen in acute bacterial infection) induced both Nox1 and Nrf2. The generation of Nox1 is IRAK-1 dependent. Low dose LPS (as seen in chronic metabolic endotoxemia) fails to induce Nrf2 and induces mild and prolonged expression of Nox1. Cells pre-challenged with low dose LPS are primed for more robust expression of ROS following a second LPS challenge. The conclusions and implications generated by this study are that chronic low dose endotoxemia (prevalent in adverse health conditions) may skew the balance of ROS generation and clearance to favor prolonged ROS accumulation, and that IRAK-1 represents a potential therapeutic target to treat chronic inflammatory diseases.
Advisors/Committee Members: Li, Liwu (committeechair), Hulver, Matthew W. (committee member), Lawrence, Christopher B. (committee member), Huckle, William R. (committee member).
Subjects/Keywords: lipopolysaccharide; IRAK-1; reactive oxygen species; innate immunity; NADPH oxidase; toll-like receptors
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APA (6th Edition):
Ringwood, L. A. (2011). Role of IRAK-1 in the Dynamic Regulation of Reactive Oxygen Species. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/77203
Chicago Manual of Style (16th Edition):
Ringwood, Lorna Ann. “Role of IRAK-1 in the Dynamic Regulation of Reactive Oxygen Species.” 2011. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/77203.
MLA Handbook (7th Edition):
Ringwood, Lorna Ann. “Role of IRAK-1 in the Dynamic Regulation of Reactive Oxygen Species.” 2011. Web. 16 Jan 2021.
Vancouver:
Ringwood LA. Role of IRAK-1 in the Dynamic Regulation of Reactive Oxygen Species. [Internet] [Doctoral dissertation]. Virginia Tech; 2011. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/77203.
Council of Science Editors:
Ringwood LA. Role of IRAK-1 in the Dynamic Regulation of Reactive Oxygen Species. [Doctoral Dissertation]. Virginia Tech; 2011. Available from: http://hdl.handle.net/10919/77203
Virginia Tech
13.
Li, Xiaoxiao.
Ranolazine: a Potential Anti-diabetic Drug.
Degree: MS, Human Nutrition, Foods, and Exercise, 2012, Virginia Tech
URL: http://hdl.handle.net/10919/19202
► Diabetes is a life-long chronic disease that affects more than 24 million Americans. Loss of pancreatic beta-cell mass and function is central to the development…
(more)
▼ Diabetes is a life-long chronic disease that affects more than 24 million Americans. Loss of pancreatic beta-cell mass and function is central to the development of both type 1 (T1D) and type 2 diabetes (T2D). Therefore, preservation or regeneration of functional beta-cell mass is one of the essential strategies to treat diabetes [1]. In my study, I tested if ranolazine, a synthetic compound, has potential to prevent or treat diabetes. Diabetes were induced in mice by giving multiple low-doses of streptozotocin (STZ). Ranolazine was given twice daily via an oral gavage (20 mg/kg) for 5 weeks. blood levels of glucose, insulin, and glycosylated hemoglobin (HbA1c) were measured. Glucose tolerance test was performed in control and treated mice. pancreatic tissues were stained with hematoxylin and eosin or stained with insulin antibody for islet mass evaluation. INS1-832/13 cells and human islets were further used to evaluate the effect of ranalozine on beta-cell survival and related signaling pathway. Fasting blood glucose levels after the fourth week of STZ injections were lower in ranolazine treated group (199.1 mg/dl) compared to the vehicle group (252.1 mg/dl) (p<0.01). HbA1c levels were reduced by ranolozine treatment (5.33%) as compared to the control group (7.23%) (p<0.05%). Glucose tolerance was improved in ranolazine treated mice (p<0.05). Mice treated with ranolazine had higher beta-cell mass (0.25%) than the vehicle group (0.07%)(p<0.01). In addition, ranolazine improved survival of human islets exposed to high levels of glucose and palmitate, whereas cell proliferation was not altered. In addition, ranolazine slightly increased the cAMP in MIN-6 cell and human islets. In conclusion, ranolazine may have therapeutic potential for diabetes by preserving beta-cell mass.
Advisors/Committee Members: Liu, Dongmin (committeechair), Hulver, Matthew W. (committee member), Jiang, Honglin (committee member), Barbeau, William E. (committee member).
Subjects/Keywords: Ranolazine; Beta-cell; Apoptosis; Proliferation; Diabetes
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APA (6th Edition):
Li, X. (2012). Ranolazine: a Potential Anti-diabetic Drug. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/19202
Chicago Manual of Style (16th Edition):
Li, Xiaoxiao. “Ranolazine: a Potential Anti-diabetic Drug.” 2012. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/19202.
MLA Handbook (7th Edition):
Li, Xiaoxiao. “Ranolazine: a Potential Anti-diabetic Drug.” 2012. Web. 16 Jan 2021.
Vancouver:
Li X. Ranolazine: a Potential Anti-diabetic Drug. [Internet] [Masters thesis]. Virginia Tech; 2012. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/19202.
Council of Science Editors:
Li X. Ranolazine: a Potential Anti-diabetic Drug. [Masters Thesis]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/19202
Virginia Tech
14.
Denko, Laura Michelle.
Cellular Reprogramming in Skeletal Muscle after Repeated Exposures to Endotoxin.
Degree: MS, Human Nutrition, Foods, and Exercise, 2012, Virginia Tech
URL: http://hdl.handle.net/10919/76808
► Obesity-related metabolic derangements have been linked to toll-like receptor 4 (TLR4), an innate immune system receptor, due to its role in proinflammatory pathways. Lipopolysaccharide (LPS),…
(more)
▼ Obesity-related metabolic derangements have been linked to toll-like receptor 4 (TLR4), an innate immune system receptor, due to its role in proinflammatory pathways. Lipopolysaccharide (LPS), a gram-negative bacteria cell wall component, is the ligand for TLR4, and has been shown to be elevated in states of metabolic disease. Heightened levels of circulating endotoxin is termed metabolic endotoxemia and has been linked to systemic inflammation which is associated with obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). Immune cells exhibit a protective ability to develop endotoxin tolerance. The objective of this study was to determine if endotoxin tolerance exists in skeletal muscle cells, and if a condition that mimics a state of over nutrition, such as elevated levels of fatty acids, affect this tolerance. To this end, L6 skeletal muscle cells were treated with low (50 pg/mL)- and high (500 ng/mL)-doses of LPS, with and without the presence of free fatty acids (FFAs). Tolerance was assessed by measuring: 1) changes in mRNA expression of interleukin-6 (IL-6) and monocyte chemoattractant-1 (MCP-1) as markers of a pro-inflammatory response; and 2) mRNA levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-°) and mitochondrial oxidative capacity via an XF24 Flux Analyzer (Seahorse Bioscience) as measures of the metabolic response. Tolerance to LPS was observed in response to low- and high-doses with MCP-1 mRNA transcription but not IL-6. Changes in PGC1-° and mitochondrial OCR exhibited a tolerant effect in response to the high dose of LPS but not the low dose. The addition of free fatty acids to LPS treatments did not prevent the tolerant effects under any conditions. In conclusion, LPS tolerance exists in skeletal muscle cells but appears to differ depending on pro-inflammatory target and LPS concentration. Additionally, fatty acids, in the current model, have no effect on LPS tolerance.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Davy, Kevin P. (committee member), Li, Liwu (committee member), Frisard, Madlyn I. (committee member).
Subjects/Keywords: TLR4; endotoxin; LPS; skeletal muscle
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APA (6th Edition):
Denko, L. M. (2012). Cellular Reprogramming in Skeletal Muscle after Repeated Exposures to Endotoxin. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/76808
Chicago Manual of Style (16th Edition):
Denko, Laura Michelle. “Cellular Reprogramming in Skeletal Muscle after Repeated Exposures to Endotoxin.” 2012. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/76808.
MLA Handbook (7th Edition):
Denko, Laura Michelle. “Cellular Reprogramming in Skeletal Muscle after Repeated Exposures to Endotoxin.” 2012. Web. 16 Jan 2021.
Vancouver:
Denko LM. Cellular Reprogramming in Skeletal Muscle after Repeated Exposures to Endotoxin. [Internet] [Masters thesis]. Virginia Tech; 2012. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/76808.
Council of Science Editors:
Denko LM. Cellular Reprogramming in Skeletal Muscle after Repeated Exposures to Endotoxin. [Masters Thesis]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/76808
15.
Mitchell, Cassie Marie.
Prebiotic supplementation with inulin and exercise influence gut microbiome composition and metabolic health.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2018, Virginia Tech
URL: http://hdl.handle.net/10919/94549
► Development of type 2 diabetes (T2D) is preceded by prediabetes, which is a metabolically "atypical" state associated with chronic low-grade inflammation, overweight and obesity, lack…
(more)
▼ Development of type 2 diabetes (T2D) is preceded by prediabetes, which is a metabolically "atypical" state associated with chronic low-grade inflammation, overweight and obesity, lack of exercise, and detrimental changes to the gut microbiome. Dietary intake and exercise are modifiable lifestyle factors for reducing T2D risk; however, several questions remain unanswered related to the efficacy and role of prebiotics and exercise, and their respective influences on gut microbiome composition, intestinal permeability, insulin sensitivity and metabolic flexibility. Sedentary to recreationally active overweight and obese adults 40-75 years old at-risk for T2D were recruited (n=22) and randomized to either supplementation with inulin, a prebiotic dietary fiber, (10g/d) or maltodextrin while consuming a controlled diet for six weeks. At baseline and week 6, participants completed a stool collection, a 4-sugar probe test, an intravenous glucose tolerance test (IVGTT), and high-fat meal challenge with skeletal muscle biopsies to evaluate changes in the gut microbiome composition, intestinal permeability, insulin sensitivity and metabolic flexibility, respectively. There were no baseline group differences (all p>0.05). Following the intervention, Bifidobacteria operational taxonomic units increased in the intervention group ([placebo: Δ9.5 ± 27.2 vs inulin: 96.3 ± 35.5][p=0.03]). There were no other group differences over time in any other outcome variables with the exception of changes in metabolic flexibility. Secondarily, a systematic review of literature was conducted to determine the influence of exercise engagement on gut microbiome composition. Overall, exercise interventions
appeared to diversify taxa within the Firmicutes phylum, and specifically in several taxa associated with butyrate production and gut barrier function. Due to unclear risk of bias in all studies and low quality of evidence, additional research is needed using well- designed trials. In summary, the respective influences of prebiotics and exercise on human gut microbiome composition and their subsequent effects on metabolic function and disease risk are not well understood.
Advisors/Committee Members: Davy, Brenda M. (committeechair), Hulver, Matthew W. (committee member), Davy, Kevin P. (committee member), Neilson, Andrew P. (committee member).
Subjects/Keywords: Prebiotics; exercise; gut microbiome; metabolic health; diabetes
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APA (6th Edition):
Mitchell, C. M. (2018). Prebiotic supplementation with inulin and exercise influence gut microbiome composition and metabolic health. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/94549
Chicago Manual of Style (16th Edition):
Mitchell, Cassie Marie. “Prebiotic supplementation with inulin and exercise influence gut microbiome composition and metabolic health.” 2018. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/94549.
MLA Handbook (7th Edition):
Mitchell, Cassie Marie. “Prebiotic supplementation with inulin and exercise influence gut microbiome composition and metabolic health.” 2018. Web. 16 Jan 2021.
Vancouver:
Mitchell CM. Prebiotic supplementation with inulin and exercise influence gut microbiome composition and metabolic health. [Internet] [Doctoral dissertation]. Virginia Tech; 2018. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/94549.
Council of Science Editors:
Mitchell CM. Prebiotic supplementation with inulin and exercise influence gut microbiome composition and metabolic health. [Doctoral Dissertation]. Virginia Tech; 2018. Available from: http://hdl.handle.net/10919/94549
Virginia Tech
16.
Marinik, Elaina.
Angiotensin II receptor blockade and insulin sensitivity in overweight and obese adults with elevated blood pressure.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2012, Virginia Tech
URL: http://hdl.handle.net/10919/37369
► Currently, it is reported that ~65% and 34% of the U.S. population is overweight and obese, respectively. Obesity is a major risk factor for cardiovascular…
(more)
▼ Currently, it is reported that ~65% and 34% of the U.S. population is overweight and obese, respectively. Obesity is a major risk factor for cardiovascular disease. Overweight and obese individuals are also at an increased risk of developing hypertension. Whole-body insulin sensitivity is reduced in obesity, resulting in insulin resistance and increased risk of type 2 diabetes. One possible mechanism contributing to insulin resistance in obesity hypertension is renin-angiotensin system (RAS) overactivation. The RAS exhibits vasocontricting and sodium-retaining properties, yet in vivo and in vitro animal experiments suggest impairment of whole-body insulin sensitivity with increased angiotensin II (Ang II) exposure. Furthermore, evidence from clinical studies indicates Ang II receptor blockers (ARBs) may reduce the incidence of new-onset diabetes compared to other antihypertensive agents in at-risk hypertensive patients. However, it is unclear if whole-body insulin sensitivity is improved with Ang II receptor blockade in humans. Thus, we tested the hypothesis that 8-week Ang II receptor blockade with olmesartan would improve whole-body insulin sensitivity in overweight and obese individuals with elevated blood pressure (BP). Olmesartan was selected for the present study because it is devoid of partial PPARγ agonist activity. To test our hypothesis, intravenous glucose tolerance tests were performed to measure insulin sensitivity before and after control and ARB treatment in a randomized crossover manner. Because skeletal muscle tissue accounts for ~75-90% of insulin-stimulated glucose uptake, a secondary exploratory aim was to examine skeletal muscle inflammatory and collagen response in relation to insulin sensitivity during ARB treatment. No baseline differences were observed between treatments (P>0.05). Both systolic (-11.7 mmHg; P=0.008) and diastolic (-12.1 mmHg; P=0.000) BP were reduced with ARB treatment. Insulin sensitivity was not different between treatments (P>0.05). No correlates of insulin sensitivity were identified. In addition, skeletal muscle inflammatory and collagen gene expression did not change from pre- to post-ARB treatment (P>0.05). Our findings suggest that short-term RAS blockade in overweight and obese adults with elevated BP does not improve whole-body insulin sensitivity, despite a significant BP reduction. Further studies are needed to clarify the role of individual RAS blockers on insulin sensitivity during RAS inhibition in obesity hypertension.
Advisors/Committee Members: Davy, Kevin P. (committeechair), Nicklas, Barbara J. (committee member), Frisard, Madlyn I. (committee member), Hulver, Matthew W. (committee member).
Subjects/Keywords: olmesartan; hypertension; renin-angiotensin system; insulin resistance; type 2 diabetes
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APA (6th Edition):
Marinik, E. (2012). Angiotensin II receptor blockade and insulin sensitivity in overweight and obese adults with elevated blood pressure. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/37369
Chicago Manual of Style (16th Edition):
Marinik, Elaina. “Angiotensin II receptor blockade and insulin sensitivity in overweight and obese adults with elevated blood pressure.” 2012. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/37369.
MLA Handbook (7th Edition):
Marinik, Elaina. “Angiotensin II receptor blockade and insulin sensitivity in overweight and obese adults with elevated blood pressure.” 2012. Web. 16 Jan 2021.
Vancouver:
Marinik E. Angiotensin II receptor blockade and insulin sensitivity in overweight and obese adults with elevated blood pressure. [Internet] [Doctoral dissertation]. Virginia Tech; 2012. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/37369.
Council of Science Editors:
Marinik E. Angiotensin II receptor blockade and insulin sensitivity in overweight and obese adults with elevated blood pressure. [Doctoral Dissertation]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/37369
Virginia Tech
17.
Zhang, Zhenhe.
The Role of Oxytocin in Bovine Satellite Cell Proliferation and Differentiation.
Degree: PhD, Animal and Poultry Sciences, 2017, Virginia Tech
URL: http://hdl.handle.net/10919/88957
► Oxytocin (OXT) is a mammalian neurohypophysial hormone. It has been demonstrated that OXT is highly expressed in skeletal muscle and satellite cell (SC) by steroid…
(more)
▼ Oxytocin (OXT) is a mammalian neurohypophysial hormone. It has been demonstrated that OXT is highly expressed in skeletal muscle and satellite cell (SC) by steroid hormone administration. However, the role of OXT in SC proliferation and differentiation is not elucidated. In this dissertation, the in-vivo and in-vitro studies are combined and used to investigate if OXT is involved in bovine SC (BSC) activity. In the in-vivo studies, we collected muscle samples from intrauterine growth restriction (IUGR) sheep, caloric restricted (CR) calves, and tamoxifen (TAM) treated heifers. In all samples, mRNA abundance of OXT was measured. For the in-vitro studies, wild-type BSC and OXT knockout BSC (CRISPR-OXT) were treated with different factors including 17β-estradiol (E2), trenbolone (TBA), TAM, OXT, and atosiban separately to investigate OXT's functions on BSC activity. For in-vivo studies, OXT expression significantly decreased (P<0.05) in IUGR, CR, and TAM muscle. In in-vitro studies, OXT alone increased (P<0.05) fusion index but not proliferation in the wild-type BSC, whereas both proliferation and differentiation were stimulated (P<0.05) by OXT treatment in the CRISPR-OXT cell. By contrast, E2 and TBA, which can stimulate OXT expression in cultured BSC, increased (P<0.05) both proliferation rate and fusion index in wild-type BSC. However, E2 and TBA only stimulated proliferation rate (P<0.05) but not fusion index for CRISPR-OXT cells. Atosiban treatment resulted in lower proliferation and differentiation (P<0.05) in both wild-type BSC and CRISPR-OXT cell compared with OXT and E2 treatment groups. Together, our studies indicate that OXT plays important roles in BSC proliferation and differentiation, and it is involved in steroid hormone stimulated BSC activity. Studies to investigate specific biological mechanisms of steroid hormone stimulated OXT expression in SC are needed in the future.
Advisors/Committee Members: Rhoads, Robert P. (committeechair), El-Kadi, Samer Wassim (committee member), Hulver, Matthew W. (committee member), Johnson, Sally E. (committee member).
Subjects/Keywords: Differentiation; Oxytocin; Proliferation; Satellite cell; Steroid hormone; Tamoxifen
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APA (6th Edition):
Zhang, Z. (2017). The Role of Oxytocin in Bovine Satellite Cell Proliferation and Differentiation. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/88957
Chicago Manual of Style (16th Edition):
Zhang, Zhenhe. “The Role of Oxytocin in Bovine Satellite Cell Proliferation and Differentiation.” 2017. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/88957.
MLA Handbook (7th Edition):
Zhang, Zhenhe. “The Role of Oxytocin in Bovine Satellite Cell Proliferation and Differentiation.” 2017. Web. 16 Jan 2021.
Vancouver:
Zhang Z. The Role of Oxytocin in Bovine Satellite Cell Proliferation and Differentiation. [Internet] [Doctoral dissertation]. Virginia Tech; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/88957.
Council of Science Editors:
Zhang Z. The Role of Oxytocin in Bovine Satellite Cell Proliferation and Differentiation. [Doctoral Dissertation]. Virginia Tech; 2017. Available from: http://hdl.handle.net/10919/88957
Virginia Tech
18.
Fu, Yu.
Baicalein, a novel anti-diabetic compound.
Degree: MS, Human Nutrition, Foods, and Exercise, 2012, Virginia Tech
URL: http://hdl.handle.net/10919/76854
► Both in type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and…
(more)
▼ Both in type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction of ?-cells, leading to the impaired insulin secretion. Thus, the search for agents to protect b-cell and enhance its function is important for diabetes treatment. Studies have reported that baicalein, a flavone originally isolated from the roots of Chinese herb Scutellaria baicalensis, has various claimed beneficial effects on health, such as anti-oxidant, anti-viral, anti-thrombotic, and anti-inflammatory effects. However, it is unclear whether it exerts an anti-diabetic action. Here, we present evidence that baicalein may be a novel anti-diabetic agent. Specifically, dietary intake of baicalein significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in high-fat diet (HFD)-fed middle-aged diabetic mice, which was associated with the improved isle t?-cell survival and mass. Baicalein treatment had no effect on food intake, body weight gain, circulating lipid profile, and insulin sensitivity in HFD-fed mice. In in-vitro studies, baicalein significantly augmented glucose-stimulated insulin secretion in insulin-secreting cells (INS1) and promotes viability of INS1 cells and human islets. These results demonstrate that baicalein may be a naturally occurring anti-diabetic agent by directly modulating pancreatic?-cell function.
Advisors/Committee Members: Liu, Dongmin (committeechair), Li, Liwu (committee member), Hulver, Matthew W. (committee member), Barbeau, William E. (committee member).
Subjects/Keywords: blood glucose; insulin; diabetes; baicalein; pancreatic?-cell
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APA (6th Edition):
Fu, Y. (2012). Baicalein, a novel anti-diabetic compound. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/76854
Chicago Manual of Style (16th Edition):
Fu, Yu. “Baicalein, a novel anti-diabetic compound.” 2012. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/76854.
MLA Handbook (7th Edition):
Fu, Yu. “Baicalein, a novel anti-diabetic compound.” 2012. Web. 16 Jan 2021.
Vancouver:
Fu Y. Baicalein, a novel anti-diabetic compound. [Internet] [Masters thesis]. Virginia Tech; 2012. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/76854.
Council of Science Editors:
Fu Y. Baicalein, a novel anti-diabetic compound. [Masters Thesis]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/76854
Virginia Tech
19.
Alkhalidy, Hana Awwad.
Flavonol kaempferol in the regulation of glucose homeostasis in diabetes.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2016, Virginia Tech
URL: http://hdl.handle.net/10919/82485
► Diabetes mellitus is a major public health concern. Although the accessible novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with…
(more)
▼ Diabetes mellitus is a major public health concern. Although the accessible novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with diabetes, the prevalence of diabetes is still rising. Type 2 diabetes (T2D) is a result of chronic insulin resistance (IR) and loss of β-cell mass and function. Therefore, the search for naturally occurring, low-cost, and safe compounds that could enhance insulin sensitivity and protect functional β-cell mass can be an effective strategy to prevent this disease. Kaempferol, a flavonol present in various medicinal herbs and edible plants, has been shown to elicit various pharmacological activities in preclinical studies. However, studies investigating the effect of kaempferol on diabetes are limited. In this dissertation, I explored the anti-diabetic potential of dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice.
First, kaempferol was supplemented in the diet to determine whether it can prevent IR and hyperglycemia in high fat (HF) diet-induced obese mice or STZ-induced obese diabetic mice. To evaluate its efficacy for treating diabetes, kaempferol was administrated once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean STZ-induced diabetic mice. The results demonstrated that long-term oral administration of kaempferol prevents HFD-induced metabolic disorders in middle-aged obese mice. Oral administration of kaempferol improved glucose intolerance and insulin sensitivity, and this effect was associated with increased Glut4 and AMPKa expression in muscle and adipose tissues. Consistent with our findings from the in iii vitro study in C2C12 muscle cell line, these findings suggest that kaempferol may reduce IR at the molecular level by improving glucose metabolism in peripheral tissues. In the second study, dietary kaempferol supplementation prevented hyperglycemia and glucose intolerance by protecting β-cell against the induced damage in obese STZ-induced diabetic mice. In the third study, the administration of kaempferol by oral gavage significantly ameliorated hyperglycemia and glucose intolerance and reduced the incidence of diabetes from 100 % to 77.8% in lean STZinduced diabetic mice. This kaempferol effect was associated with reduced hepatic glucose production, the primary
contributor to hyperglycemia, and increased glucose oxidation in the muscle of diabetic mice. Kaempferol treatment restored hexokinase activity in the liver and skeletal muscle and reduced pyruvate carboxylase (PC) activity and glycogenolysis in the liver.
Unlike its effect on T2D mice, kaempferol effect in lean STZ-induced diabetic mice was not associated with changes in plasma insulin levels. In the last study, we found that administration of kaempferol by oral gavage significantly improved blood glucose control by suppressing hepatic glucose production and improving glucose intolerance in obese insulin-resistant mice. Similar to its effect in old obese mice, kaempferol…
Advisors/Committee Members: Liu, Dongmin (committeechair), Jiang, Honglin (committee member), Good, Deborah J. (committee member), Hulver, Matthew W. (committee member).
Subjects/Keywords: Kaempferol; diabetes; glucose control; β-cells; insulin resistance; glucose production
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APA (6th Edition):
Alkhalidy, H. A. (2016). Flavonol kaempferol in the regulation of glucose homeostasis in diabetes. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/82485
Chicago Manual of Style (16th Edition):
Alkhalidy, Hana Awwad. “Flavonol kaempferol in the regulation of glucose homeostasis in diabetes.” 2016. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/82485.
MLA Handbook (7th Edition):
Alkhalidy, Hana Awwad. “Flavonol kaempferol in the regulation of glucose homeostasis in diabetes.” 2016. Web. 16 Jan 2021.
Vancouver:
Alkhalidy HA. Flavonol kaempferol in the regulation of glucose homeostasis in diabetes. [Internet] [Doctoral dissertation]. Virginia Tech; 2016. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/82485.
Council of Science Editors:
Alkhalidy HA. Flavonol kaempferol in the regulation of glucose homeostasis in diabetes. [Doctoral Dissertation]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/82485
20.
Moore, William Thomas.
Small molecule kaempferol, a novel regulator of glucose homeostasis in diabetes.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2017, Virginia Tech
URL: http://hdl.handle.net/10919/80946
► Diabetes mellitus is a growing public health concern, presently affecting 25.8 million or 8.3% of the American population. While the availability of novel drugs, techniques,…
(more)
▼ Diabetes mellitus is a growing public health concern, presently affecting 25.8 million or 8.3% of the American population. While the availability of novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with diabetes, the prevalence of diabetes is still rising. Type 2 diabetes (T2D) is a result of chronic insulin resistance and loss of -cell mass and function, and it is is always associated with the impairment in energy metabolism, causing increased intracellular fat content in skeletal muscle (SkM), liver, fat, as well as pancreatic islets. As such, the search for novel agents that simultaneously promotes insulin sensitivity and 𝜷-cell survival may provide a more effective strategy to prevent the onset and progression of this disease. Kaempferol is a flavonol that has been identified in many plants and used in traditional medicine. It has been shown to elicit various pharmacological activities in epidemiological and preclinical studies. However, to date, the studies regarding its effect on the pathogenesis of diabetes are very limited. In this dissertation, I explored the anti-diabetic potential of the dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice.
For the first animal study, kaempferol was supplemented in the diet to determine whether it can prevent insulin resistance and hyperglycemia in high fat (HF) diet-induced obese mice or STZ-induced obese diabetic mice. For the second animal study, kaempferol was administrated once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean STZ-induced diabetic mice to evaluate its efficacy for treating diabetes and further determining the underlying mechanism. The results demonstrated that dietary intake of kaempferol for 5 months (mo) improved insulin sensitivity and glucose tolerances, which were associated with increased Glut4 and AMPKα expression in muscle and adipose tissues in middle-aged mice fed a high-fat (HF) diet. In vitro, kaempferol increased lipolysis and restored chronic high fatty acid-impaired glucose uptake and glycogen synthesis in SkM cells, which were associated with improved AMPKα activity and Glut4 expression. In addition, dietary kaempferol treatment preserved functional pancreatic 𝜷-cell mass and prevented hyperglycemia and glucose intolerance in STZ-induced diabetic mice. Data from the second study show that oral administration of kaempferol significantly improved blood glucose control in obese mice, which was associated with reduced hepatic glucose production and improved whole body insulin sensitivity without altering body weight gain, food consumption, or the adiposity. In addition, kaempferol treatment increased Akt and hexokinase activity, but decreased pyruvate carboxylase and glucose-6 phosphatase activity in the liver homogenate without altering their protein expression. Consistently, kaempferol decreased pyruvate carboxylase activity and suppressed gluconeogenesis in HepG2 cells as well as primary hepatocytes isolated from the…
Advisors/Committee Members: Liu, Dongmin (committeechair), Neilson, Andrew P. (committee member), Ju, Young Hwa (committee member), Cheng, Zhiyong (committee member), Hulver, Matthew W. (committee member).
Subjects/Keywords: Kaempferol; diabetes; glucose control; skeletal muscle cells; insulin resistance; gluconeogenesis
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APA (6th Edition):
Moore, W. T. (2017). Small molecule kaempferol, a novel regulator of glucose homeostasis in diabetes. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/80946
Chicago Manual of Style (16th Edition):
Moore, William Thomas. “Small molecule kaempferol, a novel regulator of glucose homeostasis in diabetes.” 2017. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/80946.
MLA Handbook (7th Edition):
Moore, William Thomas. “Small molecule kaempferol, a novel regulator of glucose homeostasis in diabetes.” 2017. Web. 16 Jan 2021.
Vancouver:
Moore WT. Small molecule kaempferol, a novel regulator of glucose homeostasis in diabetes. [Internet] [Doctoral dissertation]. Virginia Tech; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/80946.
Council of Science Editors:
Moore WT. Small molecule kaempferol, a novel regulator of glucose homeostasis in diabetes. [Doctoral Dissertation]. Virginia Tech; 2017. Available from: http://hdl.handle.net/10919/80946
Virginia Tech
21.
Stevens, Joseph R.
The Effects of Low Dose Endotoxin on Glucose Homeostasis.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2014, Virginia Tech
URL: http://hdl.handle.net/10919/64849
► Obese individuals present with an increased inflammatory tone as compared to healthy, normal-weight individuals, which is associated with insulin resistance. One factor hypothesized to contribute…
(more)
▼ Obese individuals present with an increased inflammatory tone as compared to healthy, normal-weight individuals, which is associated with insulin resistance. One factor hypothesized to contribute to increased inflammation in obese and diabetic states is elevated blood endotoxin levels, also known as metabolic endotoxemia. In healthy rodents (non-obese and insulin sensitive), there is evidence that blood endotoxin levels fluctuate over the course of the day with elevations in the post-prandial state that return to baseline levels in the post-absorptive state. High-fat feeding in these animals altered these fluctuations causing endotoxin levels to remain high throughout the day. The effects of alterations in endotoxin levels on glucose metabolism are not understood. The goal of this study was to determine the effects of short-term and long-term increases in endotoxin of a low magnitude on insulin signaling in a human primary cell line as well as the effects of short-term endotoxin treatments on glucose homeostasis in a C57/Bl6 mouse model. First, we tested the hypothesis in cell culture that short-term low-dose endotoxin treatments would enhance insulin-signaling and glycogen synthesis while long-term treatments would have inhibitory effects. Under our second hypothesis, we examined whether short-term low-dose treatments of endotoxin would contribute to improvements in glucose tolerance in a mouse model. In contrast to our first hypothesis, short-term endotoxin treatments did not improve insulin signaling or glycogen synthesis although long-term treatments did contribute to decreases in glycogen synthesis. Interestingly, short-term endotoxin treatments resulted in significant improvements in glucose clearance in the mouse model; this is believed to be partly attributed to LPS inhibiting gluconeogenesis. Future studies are necessary to understand the mechanisms responsible for altered glucose metabolism in response to low magnitude changes in LPS levels.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Frisard, Madlyn I. (committee member), Davy, Kevin P. (committee member), Grange, Robert W. (committee member), Li, Liwu (committee member).
Subjects/Keywords: Endotoxin; Inflammation; Glucose Metabolism
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APA (6th Edition):
Stevens, J. R. (2014). The Effects of Low Dose Endotoxin on Glucose Homeostasis. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/64849
Chicago Manual of Style (16th Edition):
Stevens, Joseph R. “The Effects of Low Dose Endotoxin on Glucose Homeostasis.” 2014. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/64849.
MLA Handbook (7th Edition):
Stevens, Joseph R. “The Effects of Low Dose Endotoxin on Glucose Homeostasis.” 2014. Web. 16 Jan 2021.
Vancouver:
Stevens JR. The Effects of Low Dose Endotoxin on Glucose Homeostasis. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/64849.
Council of Science Editors:
Stevens JR. The Effects of Low Dose Endotoxin on Glucose Homeostasis. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/64849
Virginia Tech
22.
Pittman, Joshua Taylor.
The Metabolic Effects of Low Grade Inflammation on Postprandial Metabolism Following a High Fat Meal.
Degree: MS, Human Nutrition, Foods, and Exercise, 2013, Virginia Tech
URL: http://hdl.handle.net/10919/51543
► Inflammation is a central feature of various metabolic diseases including obesity and type-II diabetes. For this study, we hypothesized postprandial metabolism following an acute, high…
(more)
▼ Inflammation is a central feature of various metabolic diseases including obesity and type-II diabetes. For this study, we hypothesized postprandial metabolism following an acute, high fat (HF) meal to be impaired in mice pre-injected with an inflammatory agonist. To this end, C57BL/6J mice were injected with saline or lipopolysaccharide (LPS, 1μg/kgbw) following an overnight fast and gavaged 2hr post-injection with water or a HF meal in liquid form (5kcal; 21.4%SF, 40.8%UF, 27.1%CHO, 10.7%PRO). Blood and muscle samples taken 3hr post-gavage underwent ex vivo analysis. Overall, results demonstrated a metabolic response to a HF meal that was blocked in the presence of LPS. Metabolic flexibility, though unchanged following the HF meal alone, was reduced following the HF meal in the presence of LPS. Additionally, state-4 uncoupled mitochondrial respiration, which was increased following the HF meal, was also reduced following the HF meal in the presence of LPS. Similar near-significant trends were also observed with total palmitate oxidation. Although no independent response to a HF meal or LPS exposure was observed, a unique interaction between treatments significantly diminished ADP dependent, state-3 and maximal respiration. These effects do not appear to be dependent on the production of reactive oxygen species (ROS) since neither the HF meal nor LPS exposure resulted in increased production of ROS. In conclusion, these results demonstrate that acute activation of inflammatory pathways results in alterations in metabolic response to a HF meal in skeletal muscle from mice, although the mechanism underlying these effects is not yet understood.
Advisors/Committee Members: Frisard, Madlyn I. (committeechair), Hulver, Matthew W. (committee member), Davy, Kevin P. (committee member), Gerrard, David E. (committee member).
Subjects/Keywords: Metabolic flexibility; inflammation; skeletal muscle; mitochondria
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APA (6th Edition):
Pittman, J. T. (2013). The Metabolic Effects of Low Grade Inflammation on Postprandial Metabolism Following a High Fat Meal. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/51543
Chicago Manual of Style (16th Edition):
Pittman, Joshua Taylor. “The Metabolic Effects of Low Grade Inflammation on Postprandial Metabolism Following a High Fat Meal.” 2013. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/51543.
MLA Handbook (7th Edition):
Pittman, Joshua Taylor. “The Metabolic Effects of Low Grade Inflammation on Postprandial Metabolism Following a High Fat Meal.” 2013. Web. 16 Jan 2021.
Vancouver:
Pittman JT. The Metabolic Effects of Low Grade Inflammation on Postprandial Metabolism Following a High Fat Meal. [Internet] [Masters thesis]. Virginia Tech; 2013. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/51543.
Council of Science Editors:
Pittman JT. The Metabolic Effects of Low Grade Inflammation on Postprandial Metabolism Following a High Fat Meal. [Masters Thesis]. Virginia Tech; 2013. Available from: http://hdl.handle.net/10919/51543
23.
Harvey, Mordecai Micah.
Characterization of an in vitro exercise model and the effects of a metabolic endotoxemia on skeletal muscle adaptation to electric pulse stimulation.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2017, Virginia Tech
URL: http://hdl.handle.net/10919/78235
► The prevalence of obesity and type II diabetes is increasing. Although exercise is widely accepted for prevention and treatment, evidence of resistance to exercise in…
(more)
▼ The prevalence of obesity and type II diabetes is increasing. Although exercise is widely accepted for prevention and treatment, evidence of resistance to exercise in patients with these diseases is also mounting. Muscle contraction during exercise stimulate cellular responses important for adaptation. These responses include the release of myokines and the subsequent increase in substrate metabolism. This study aimed to define a culture model for simulating exercise in human primary skeletal muscle cells. We hypothesized that chronic electric pulse stimulation (EPS) of human myotubes in vitro would emulate cellular and molecular responses to exercise observed in vivo. To define this model, we applied EPS to human myotubes for varied lengths of time and measured interleukin-6 (Il-6), peroxisome proliferator-activated receptor gamma coactivator 1- (PGC1-), superoxide dismutase 2 (SOD2), substrate metabolism, metabolic enzyme activity, heat stress markers, and pH. To recreate the inflammatory milieu observed in metabolic disease states we treated the myotubes with a low dose of 20 EU lipopolysaccharide (LPS). Following the 24-hour stimulation we observed significant increases in transcription of Il-6, PGC1-, and SOD2. Basal glucose and fatty acid oxidation were also markedly increased in the cells after EPS. Cells treated with LPS elicited a blunted transcriptional, metabolic, and enzymatic response to EPS. These findings suggest that EPS is a viable model for simulating the effects of exercise. Our observations also indicate that an inflammatory environment could play a role in interfering with the adaptations to exercise.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Frisard, Madlyn I. (committee member), Davy, Kevin P. (committee member), Grange, Robert W. (committee member), Li, Liwu (committee member).
Subjects/Keywords: endotoxemia; skeletal; muscle; exercise; electric; stimulation
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APA (6th Edition):
Harvey, M. M. (2017). Characterization of an in vitro exercise model and the effects of a metabolic endotoxemia on skeletal muscle adaptation to electric pulse stimulation. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/78235
Chicago Manual of Style (16th Edition):
Harvey, Mordecai Micah. “Characterization of an in vitro exercise model and the effects of a metabolic endotoxemia on skeletal muscle adaptation to electric pulse stimulation.” 2017. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/78235.
MLA Handbook (7th Edition):
Harvey, Mordecai Micah. “Characterization of an in vitro exercise model and the effects of a metabolic endotoxemia on skeletal muscle adaptation to electric pulse stimulation.” 2017. Web. 16 Jan 2021.
Vancouver:
Harvey MM. Characterization of an in vitro exercise model and the effects of a metabolic endotoxemia on skeletal muscle adaptation to electric pulse stimulation. [Internet] [Doctoral dissertation]. Virginia Tech; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/78235.
Council of Science Editors:
Harvey MM. Characterization of an in vitro exercise model and the effects of a metabolic endotoxemia on skeletal muscle adaptation to electric pulse stimulation. [Doctoral Dissertation]. Virginia Tech; 2017. Available from: http://hdl.handle.net/10919/78235
24.
Hayes, Jasmine Marie.
Skeletal Muscle Adaption to 5 days of High-Fat Feeding in Humans.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2018, Virginia Tech
URL: http://hdl.handle.net/10919/85059
► Skeletal muscle is highly involved in macronutrient metabolism. To maintain proper energy metabolism and physiology, skeletal muscle must adapt to nutrient supply. Thus, diet macronutrient…
(more)
▼ Skeletal muscle is highly involved in macronutrient metabolism. To maintain proper energy metabolism and physiology, skeletal muscle must adapt to nutrient supply. Thus, diet macronutrient composition is an important modulator of skeletal muscle metabolism. Evidence from rodent and human models show high-fat diets contribute to impaired insulin signaling, as well as decreased fatty acid and glucose oxidation. Utilizing proteomic analysis of metabolic proteins in humans may lead to the mechanism behind skeletal muscle adaption to macronutrient composition, potentially providing the groundwork for characterizing the etiology of high-fat feeding induced metabolic disease. The objective of this study was to compare the substrate oxidation patterns and the levels of metabolic proteins in the fasted skeletal muscle of lean, healthy males that either increased fatty acid oxidation in response to the high-fat diet, termed responders, or males that decreased fatty acid oxidation, termed non-responders. We employed a controlled feeding study design, where the participants served as their own controls. Following a 2-week control diet (30% fat, 55% carbohydrate and 15% protein), participants came to the lab fasted overnight and a muscle biopsy was taken from their vastus lateralis muscle. Participants were then placed on a 5-day high-fat diet (50% fat [45% saturated fat], 35% carbohydrate, and 15% protein). Following this diet, participants again came to the lab fasted overnight and another muscle biopsy was taken from their vastus lateralis muscle. Both the control and the high-fat diets were isocaloric to habitual diets. Muscle from the biopsies were utilized for substrate metabolism measures and mass spectrometry. We did not observe any significant differences in glucose oxidation between responders and non-responders, prior to or following the high-fat diet. Our proteomic analysis identified 81 proteins and protein subunits involved in substrate metabolism but only 6 were differentially regulated by the high-fat diet. Independent of the high-fat diet, compared to non-responders, responders contained an overall higher content of protein subunits belonging to Complex I and ATP synthase. The findings from this study suggest that adaption to high-fat feeding is individual specific and proteomic changes alone cannot explain high-fat feeding induced metabolic changes.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Frisard, Madlyn I. (committee member), Helm, Richard F. (committee member), Davy, Kevin P. (committee member).
Subjects/Keywords: High-fat diet; metabolism; skeletal muscle
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APA (6th Edition):
Hayes, J. M. (2018). Skeletal Muscle Adaption to 5 days of High-Fat Feeding in Humans. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/85059
Chicago Manual of Style (16th Edition):
Hayes, Jasmine Marie. “Skeletal Muscle Adaption to 5 days of High-Fat Feeding in Humans.” 2018. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/85059.
MLA Handbook (7th Edition):
Hayes, Jasmine Marie. “Skeletal Muscle Adaption to 5 days of High-Fat Feeding in Humans.” 2018. Web. 16 Jan 2021.
Vancouver:
Hayes JM. Skeletal Muscle Adaption to 5 days of High-Fat Feeding in Humans. [Internet] [Doctoral dissertation]. Virginia Tech; 2018. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/85059.
Council of Science Editors:
Hayes JM. Skeletal Muscle Adaption to 5 days of High-Fat Feeding in Humans. [Doctoral Dissertation]. Virginia Tech; 2018. Available from: http://hdl.handle.net/10919/85059
Virginia Tech
25.
Osterberg, Kristin.
The Effect of a Probiotic Supplement on Insulin Sensitivity and Skeletal Muscle Substrate Oxidation during High Fat Feeding.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2014, Virginia Tech
URL: http://hdl.handle.net/10919/64848
► Background: Modifying the gut microbiota through the administration of probiotics during high fat feeding has been shown to attenuate weight gain and body fat accretion…
(more)
▼ Background: Modifying the gut microbiota through the administration of probiotics during high fat feeding has been shown to attenuate weight gain and body fat accretion while improving insulin sensitivity in animal models.
Objective: Our objective was to determine the effects of the probiotic VSL#3 on body weightand composition, skeletal muscle substrate oxidation, and insulin sensitivity and during 4 weeks of high-fat, hypercaloric feeding. We hypothesized that the probiotic would attenuate the body weight and fat gain and adverse changes in insulin sensitivity and substrate oxidation following high fat, hypercaloric feeding in young, non-obese males.
Methods: Twenty non-obese males (18-30 y) volunteered to participate in the present study. Following a 2-week eucaloric control diet, subjects underwent a dual x-ray absorptiometry (DXA) to determine body composition, an intravenous glucose tolerance test (IVGTT) to determine insulin sensitivity, a skeletal muscle biopsy for measurement of substrate oxidation. Serum endotoxin was also measured. Subsequently, subjects were randomized to receive either VSL#3 (2 satchets) or placebo during 4 weeks of consuming a high fat (55% fat), hypercaloric diet (+1,000 kcal/day). Macronutrient composition of the high fat diet was 55% fat, 30% carbohydrate, and 15% protein.
Results: There were no differences between the groups in subject characteristics or in the dependent variables at baseline. Body weight and fat mass increased less (P<0.045) following the high fat diet with VSL#3 compared to placebo. Insulin sensitivity (and other IVGTT variables) and both glucose and fat oxidation did not change significantly with time or VSL#3 treatment. Serum endotoxin concentration was not different between groups following the high-fat diet.
Conclusions: VSL#3, a multi-strain probiotic, attenuated body weight and fat gain following a 4-week high fat, hypercaloric diet compared with a placebo. There were no differences between the VSL and control in circulating endotoxin, insulin sensitivity (and other IVGTT variables) or in skeletal muscle substrate oxidation.
Advisors/Committee Members: Davy, Kevin P. (committeechair), Melby, Christopher L. (committee member), Hulver, Matthew W. (committee member), Frisard, Madlyn I. (committee member).
Subjects/Keywords: probiotic; high fat diet; insulin sensitivity; substrate oxidation
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APA (6th Edition):
Osterberg, K. (2014). The Effect of a Probiotic Supplement on Insulin Sensitivity and Skeletal Muscle Substrate Oxidation during High Fat Feeding. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/64848
Chicago Manual of Style (16th Edition):
Osterberg, Kristin. “The Effect of a Probiotic Supplement on Insulin Sensitivity and Skeletal Muscle Substrate Oxidation during High Fat Feeding.” 2014. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/64848.
MLA Handbook (7th Edition):
Osterberg, Kristin. “The Effect of a Probiotic Supplement on Insulin Sensitivity and Skeletal Muscle Substrate Oxidation during High Fat Feeding.” 2014. Web. 16 Jan 2021.
Vancouver:
Osterberg K. The Effect of a Probiotic Supplement on Insulin Sensitivity and Skeletal Muscle Substrate Oxidation during High Fat Feeding. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/64848.
Council of Science Editors:
Osterberg K. The Effect of a Probiotic Supplement on Insulin Sensitivity and Skeletal Muscle Substrate Oxidation during High Fat Feeding. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/64848
Virginia Tech
26.
Shabrokh, Elika.
Mitochondrial Biology in Sporadic Inclusion Body Myositis.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2014, Virginia Tech
URL: http://hdl.handle.net/10919/47782
► Sporadic Inclusion Body Myositis (sIBM) is an inflammatory muscle disease that strikes individuals at random and accounts for approximately 1/3 of all idiopathic inflammatory myopathies.…
(more)
▼ Sporadic Inclusion Body Myositis (sIBM) is an inflammatory muscle disease that strikes individuals at random and accounts for approximately 1/3 of all idiopathic inflammatory myopathies. It is characterized by progressive weakness of distal and proximal muscles and is the most common muscle disorder in individuals over 50 years of age. Currently, there is no known cause, cure, or enduring treatment for sIBM, although a number of theories as to its cause have been proposed. One theory proposes that activation of the inflammatory/ immune response is the primary trigger resulting in muscle degeneration and protein abnormalities, while an alternative theory suggests that sIBM is a degenerative muscle disease with abnormal pathogenic protein accumulation, in particular Abeta, being a primary cause that triggers an inflammatory/ immune response. Mitochondrial abnormalities have been observed in skeletal muscle from patients diagnosed with the disease, however the role of the mitochondria in disease pathology is still unclear. The aim of this dissertation was to evaluate: 1) the role of the mitochondria in the development of sIBM and 2) the role of amyloid beta on mitochondrial function in skeletal muscle. A better understanding of the role of the mitochondria in the development of sIBM may help to identify novel prevention and/ or treatment strategies.
Advisors/Committee Members: Frisard, Madlyn I. (committeechair), Davy, Kevin P. (committee member), Helm, Richard F. (committee member), Hulver, Matthew W. (committee member).
Subjects/Keywords: Amyloid beta; Inclusion Body Myositis; Mitochondria
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APA (6th Edition):
Shabrokh, E. (2014). Mitochondrial Biology in Sporadic Inclusion Body Myositis. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/47782
Chicago Manual of Style (16th Edition):
Shabrokh, Elika. “Mitochondrial Biology in Sporadic Inclusion Body Myositis.” 2014. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/47782.
MLA Handbook (7th Edition):
Shabrokh, Elika. “Mitochondrial Biology in Sporadic Inclusion Body Myositis.” 2014. Web. 16 Jan 2021.
Vancouver:
Shabrokh E. Mitochondrial Biology in Sporadic Inclusion Body Myositis. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/47782.
Council of Science Editors:
Shabrokh E. Mitochondrial Biology in Sporadic Inclusion Body Myositis. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/47782
Virginia Tech
27.
Angiletta, Chris.
The Role of Fasting Acylcarnitines in Metabolic Flexibility from Short Term High Fat Feeding.
Degree: MS, Human Nutrition, Foods, and Exercise, 2018, Virginia Tech
URL: http://hdl.handle.net/10919/82401
► Metabolic flexibility plays a significant role in energy homeostasis by regulating fuel selection in correspondence to energy demand. Obese and type II diabetic populations have…
(more)
▼ Metabolic flexibility plays a significant role in energy homeostasis by regulating fuel selection in correspondence to energy demand. Obese and type II diabetic populations have displayed a hindered ability to properly transition from fat oxidation while in a fasted state to carbohydrate oxidation once fed, leading to a buildup of mitochondrial metabolites such as acylcarnitines. Carnitine, essential for fatty acyl-CoA transport through the inner and outer mitochondrial membranes, can be an indicator of mitochondrial distress as elevated levels tend to spill over into plasma suggesting a disruption in oxidation. The current study was designed to examine the effect of short term, high fat feeding on plasma acylcarnitine species diversity and levels and if acylcarnitines are associated with metabolic flexibility. 13 healthy, non-obese, sedentary males, aged 18-40 years participated in this study. Following a 12-hour overnight fast a biopsy was taken from the quadricep before and 4 hours after a high fat meal. Blood draws were obtained pre-biopsy while fasted and every hour for 4 hours post high fat meal consumption. Acylcarnitines from plasma were converted to their butyl esters and analyzed by electrospray ionization tandem mass spectrometry (MS/MS). Changes were observed in acetylcarntine (P=0.0125), glucose oxidation (P=0.0295), C16:1/C16:0 desaturation index (P= 0.0397), and C18:1/C18:0 desaturation index (P=0.0012). We did not find that individual changes in flexibility correlated with circulating acylcarnitine measurements in a fasted state
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Frisard, Madlyn I. (committee member), Davy, Kevin P. (committee member), Neilson, Andrew P. (committee member).
Subjects/Keywords: Metabolic flexibility; acylcarnitines; carnitine; high fat diet
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APA (6th Edition):
Angiletta, C. (2018). The Role of Fasting Acylcarnitines in Metabolic Flexibility from Short Term High Fat Feeding. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/82401
Chicago Manual of Style (16th Edition):
Angiletta, Chris. “The Role of Fasting Acylcarnitines in Metabolic Flexibility from Short Term High Fat Feeding.” 2018. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/82401.
MLA Handbook (7th Edition):
Angiletta, Chris. “The Role of Fasting Acylcarnitines in Metabolic Flexibility from Short Term High Fat Feeding.” 2018. Web. 16 Jan 2021.
Vancouver:
Angiletta C. The Role of Fasting Acylcarnitines in Metabolic Flexibility from Short Term High Fat Feeding. [Internet] [Masters thesis]. Virginia Tech; 2018. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/82401.
Council of Science Editors:
Angiletta C. The Role of Fasting Acylcarnitines in Metabolic Flexibility from Short Term High Fat Feeding. [Masters Thesis]. Virginia Tech; 2018. Available from: http://hdl.handle.net/10919/82401
28.
Vashro, Taylor Nadine.
The effect of mung bean on improving dietary diversity in women and children in Senegal.
Degree: MS, Human Nutrition, Foods, and Exercise, 2017, Virginia Tech
URL: http://hdl.handle.net/10919/86361
► Since 2015, a U.S. Agency for International Development and Virginia Tech Education and Research in Agriculture collaboration has introduced and tested mung bean as a…
(more)
▼ Since 2015, a U.S. Agency for International Development and
Virginia Tech Education and Research in Agriculture collaboration has introduced and tested mung bean as a potential crop to alleviate malnutrition and food insecurity in Senegal. This MS thesis describes a study conducted to assess the impact of mung bean on dietary diversity of Senegalese women and children in the Kaolack, Matam and Bakel localities of Senegal. A mixed-methods research approach included individual surveys to determine dietary diversity scores (DDS) and focus groups to assess the perceived impacts of mung bean. The dietary diversity survey was conducted with 194 participants including adult women, ages 15 to 70 years (n=109) and children, ages 0-10 years (n=85). Half (52%) of the population were mung bean consumers. The dietary diversity surveys revealed an average DDS of 5.73 on a scale of one to 10, with 5.83 and 5.62 for mung bean and non-mung bean consuming groups, respectively. There was a statistically significant difference in DDS between mung-bean consuming women and both mung bean and non-mung bean children, and between mung bean and non-mung bean consumers in Bakel; however, there was no significant difference between overall mung bean and non-mung bean groups DDS. Focus groups (n=11) with mung bean consuming women identified perceived agricultural, health, and financial benefits associated with mung bean consumption. These results can increase our understanding of how mung bean may influence policy-relevant issues for the Senegalese population, including agricultural, health and financial outcomes that are not reflected in dietary diversity surveys.
Advisors/Committee Members: Hulver, Matthew W. (committeechair), Farris, Alisha (committee member), Kraak, Vivica (committee member), Abaye, Azenegashe Ozzie (committee member).
Subjects/Keywords: Mung bean; Dietary diversity; Mixed method research; Senegal; Food security
…individual, community, and policy interventions.4 In 2012, a
USAID Virginia Tech collaboration for…
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APA (6th Edition):
Vashro, T. N. (2017). The effect of mung bean on improving dietary diversity in women and children in Senegal. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/86361
Chicago Manual of Style (16th Edition):
Vashro, Taylor Nadine. “The effect of mung bean on improving dietary diversity in women and children in Senegal.” 2017. Masters Thesis, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/86361.
MLA Handbook (7th Edition):
Vashro, Taylor Nadine. “The effect of mung bean on improving dietary diversity in women and children in Senegal.” 2017. Web. 16 Jan 2021.
Vancouver:
Vashro TN. The effect of mung bean on improving dietary diversity in women and children in Senegal. [Internet] [Masters thesis]. Virginia Tech; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/86361.
Council of Science Editors:
Vashro TN. The effect of mung bean on improving dietary diversity in women and children in Senegal. [Masters Thesis]. Virginia Tech; 2017. Available from: http://hdl.handle.net/10919/86361
29.
Baker, Bianca Nicole.
Molecular and Cellular Mechanisms Responsible for Low-grade Stress and Inflammation Triggered By Super-low Dose Endotoxin.
Degree: PhD, Biological Sciences, 2014, Virginia Tech
URL: http://hdl.handle.net/10919/56732
► The gram-negative endotoxin, lipopolysaccharide (LPS), has been extensively researched in high doses (10-200ng/ml) and is well-documented in the literature for its ability to result in…
(more)
▼ The gram-negative endotoxin, lipopolysaccharide (LPS), has been extensively researched in high doses (10-200ng/ml) and is well-documented in the literature for its ability to result in devastating effects such as multi-organ failure, sepsis, and septic shock. In high doses, LPS signals through Toll-like-receptor 4 (TLR4) and triggers a cascade of events culminating in the release of pro- and anti-inflammatory cytokines and the activation of NF-κB. In contrast, super-low doses of LPS (1-100pg/ml) are able to trigger the persistent release of pro-inflammatory mediators while evading the compensatory activation of NF-κB. This mild yet persistent induction of inflammation may lie at the heart of numerous inflammatory diseases and disorders and warrants studies such as this to elucidate the novel mechanisms. In this study, we explored the novel mechanisms utilized by super-low dose LPS in cellular stress and low-grade inflammation.
In the first study, the molecular mechanisms governing the role of super-low dose LPS on cellular stress and necroptosis were examined. We show that in the presence of super-low dose LPS (50pg/ml), the key regulators of mitochondrial fission and fusion, Drp1 and Mfn1 respectively, are inversely regulated. An increase in mitochondrial fragmentation and cell death which was not dependent on caspase activation was observed. In addition, super-low dose LPS was able to activate RIP3, a kinase
responsible for inducing the inflammatory cell death, necroptosis. These mechanisms were regulated in an Interleukin-1 receptor-associated kinase 1 (IRAK-1) dependent manner.
In the second study, the molecular mechanisms governing the role of super-low dose LPS on cellular stress and endosome/lysosome fusion were examined. In the presence of low-dose LPS (50pg/ml), endosomal-lysosomal fusion is inhibited and a loss of endosomal acidification required for the successful clearance of cellular debris and resolution of inflammation was observed. Additionally, super-low dose LPS induced the accumulation of p62 indicative of the suppression of autophagy. Tollip and Interleukin-1 receptor-associated kinase 3 (IRAK-M) appear to be critical regulators in this process.
Collectively, these studies show that low-dose endotoxemia is capable of causing persistent cellular stress, not observed in the presence of high-dose LPS (10-200ng/ml), and that it promotes necroptotic cell death while suppressing mechanisms necessary for the resolution of inflammation such as endosome-lysosome fusion. This research reveals novel mechanisms utilized by low-dose endotoxemia which could aid future efforts to develop prevention and treatment for various debilitating inflammatory diseases.
Advisors/Committee Members: Li, Liwu (committeechair), Subbiah, Elankumaran (committee member), Hulver, Matthew W. (committee member), Schubot, Florian D. (committee member).
Subjects/Keywords: Lipopolysaccharide; inflammation; cell death; mitochondrial dynamics; endosome-lysosome fusion
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APA (6th Edition):
Baker, B. N. (2014). Molecular and Cellular Mechanisms Responsible for Low-grade Stress and Inflammation Triggered By Super-low Dose Endotoxin. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/56732
Chicago Manual of Style (16th Edition):
Baker, Bianca Nicole. “Molecular and Cellular Mechanisms Responsible for Low-grade Stress and Inflammation Triggered By Super-low Dose Endotoxin.” 2014. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/56732.
MLA Handbook (7th Edition):
Baker, Bianca Nicole. “Molecular and Cellular Mechanisms Responsible for Low-grade Stress and Inflammation Triggered By Super-low Dose Endotoxin.” 2014. Web. 16 Jan 2021.
Vancouver:
Baker BN. Molecular and Cellular Mechanisms Responsible for Low-grade Stress and Inflammation Triggered By Super-low Dose Endotoxin. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/56732.
Council of Science Editors:
Baker BN. Molecular and Cellular Mechanisms Responsible for Low-grade Stress and Inflammation Triggered By Super-low Dose Endotoxin. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/56732
30.
Baugh, Mary Elizabeth.
Skeletal Muscle Substrate Metabolism following a High Fat Diet in Sedentary and Endurance Trained Males.
Degree: PhD, Human Nutrition, Foods, and Exercise, 2018, Virginia Tech
URL: http://hdl.handle.net/10919/85417
► Insulin resistance (IR), T2DM, and obesity together form a cluster of interrelated metabolic challenges that may be linked by metabolic inflexibility. Metabolic inflexibility is characterized…
(more)
▼ Insulin resistance (IR), T2DM, and obesity together form a cluster of interrelated metabolic challenges that may be linked by metabolic inflexibility. Metabolic inflexibility is characterized by the resistance to switching substrate oxidation preference based on substrate availability and can be measured in either fasted or insulin-stimulated conditions. As the largest site for glucose disposal and a primary tissue influencing regulation of blood glucose concentrations, skeletal muscle likely plays a central role in regulating substrate oxidation preference based on substrate availability. Skeletal muscle lipotoxicity caused by an impaired regulation of fat uptake and oxidation is postulated to disrupt insulin signaling and lead to skeletal muscle IR. High dietary saturated fat intake results in reduced basal fat oxidation and a resistance to switching to carbohydrate oxidation during insulin-stimulated conditions in susceptible individuals. This metabolic inflexibility may lead to an accumulation of intramyocellular species that impair insulin signaling. Endurance exercise training improves the capacity for fat oxidation in metabolically inflexible individuals. However, relatively little is known about how endurance exercise training influences substrate oxidation preference when paired with a high fat diet (HFD). Therefore, the purpose of this study was to determine the effects of a HFD on substrate metabolism in skeletal muscle of sedentary and endurance trained (ET) males. Healthy, sedentary (n=17) and ET (n=7) males first consumed a 10-day moderate carbohydrate diet (55% carbohydrate, 30% total fat, <10% saturated fat) isocaloric to their individual energy requirements and then underwent a 4- hour high fat challenge testing session. During the session, they consumed a high fat meal (820 kcals; 25% carbohydrate, 63% total fat [26% saturated fat]), and skeletal muscle biopsies were taken in the fasted and 4-hour postprandial conditions. Participants then consumed a 5-day HFD (30% carbohydrate, 55% total fat, 25% saturated fat) and repeated the high fat challenge testing session. Substrate oxidation measures were performed on the collected skeletal muscle tissue, and the meal effect, defined as the percent change from the fasting to 4- hour postprandial condition, for each measure was calculated. There was a HFD by physical activity group interaction on meal effect for metabolic flexibility (P<0.05) and a HFD effect on meal effect for glucose oxidation (P<0.05). Meal effects for metabolic flexibility and glucose oxidation were maintained in the ET (20 ± 4% to 41 ± 21% and 128 ± 92% and 41 ± 15%, respectively; both P>0.05) but decreased in the sedentary (34 ± 7% to 4 ± 5% and 78 ± 26% to -21 ± 6%, respectively; both P<0.01) group. There were trends toward HFD effects on reductions in meal effects for total (P=0.062) and incomplete (P=0.075) fat oxidation, which were driven primarily by an increase in fasting total (12.1 ± 2.6 nmol/mg protein/h to 18.5 ± 2.3 nmol/mg protein/h; P<0.01) and incomplete (11.5 ± 2.5…
Advisors/Committee Members: Davy, Kevin P. (committeechair), Davy, Brenda M. (committee member), Helm, Richard F. (committee member), Hulver, Matthew W. (committee member).
Subjects/Keywords: substrate metabolism; high fat diet; exercise; endurance training; metabolic flexibility
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
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Manager
APA (6th Edition):
Baugh, M. E. (2018). Skeletal Muscle Substrate Metabolism following a High Fat Diet in Sedentary and Endurance Trained Males. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/85417
Chicago Manual of Style (16th Edition):
Baugh, Mary Elizabeth. “Skeletal Muscle Substrate Metabolism following a High Fat Diet in Sedentary and Endurance Trained Males.” 2018. Doctoral Dissertation, Virginia Tech. Accessed January 16, 2021.
http://hdl.handle.net/10919/85417.
MLA Handbook (7th Edition):
Baugh, Mary Elizabeth. “Skeletal Muscle Substrate Metabolism following a High Fat Diet in Sedentary and Endurance Trained Males.” 2018. Web. 16 Jan 2021.
Vancouver:
Baugh ME. Skeletal Muscle Substrate Metabolism following a High Fat Diet in Sedentary and Endurance Trained Males. [Internet] [Doctoral dissertation]. Virginia Tech; 2018. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10919/85417.
Council of Science Editors:
Baugh ME. Skeletal Muscle Substrate Metabolism following a High Fat Diet in Sedentary and Endurance Trained Males. [Doctoral Dissertation]. Virginia Tech; 2018. Available from: http://hdl.handle.net/10919/85417
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Open Access Theses and Dissertations
