subject:(myokines)

NSYSU

1. Shen, Ying-Ying. Generation and Characterization of Recombinant Adenovirus Encoding Irisin.

Degree: Master, Institute of Biomedical Sciences, 2017, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0722117-235342

► Exercise represents one of the most effective approaches for control of obesity and metabolic syndromes. Irisin is a 112-residue myokine secreted by skeletal muscle through… (more)

▼ Exercise represents one of the most effective approaches for control of obesity and metabolic syndromes. Irisin is a 112-residue myokine secreted by skeletal muscle through proteolytical cleavage from its precursor fibronectin type III domain containing 5 (FNDC5). Irisin stimulates brown fat-like development from white fat and thermogenesis through increasing mitochondria genesis and energy expenditure, thereby reducing body weight and insulin resistance. Because of its anti-obesity effects and evolutionary conservation, Irisin has been proposed as a promising therapeutic agent for metabolic diseases since its discovery in 2012. To combat the obesity syndrome, gene therapy approached may be required for long-term management of patients with metabolic diseases. Thus, the present study aims to generate the recombinant adenovirus vectors for Irisin production in various types of cells/organs, thereby evaluating their therapeutic potential and mechanism. Recombinant irisin was expressed and purified from E. coli with an apparent molecular weight of 14 kDa. The anti-irisin antibody was raised by periodical injection of recombinant irisin into rabbit and purified from serum using protein G Sepharose affinity chromatography. For gene delivery, adenovirus vector encoding FNDC5 (Ad-FNDC5) and irisin (Ad-irisin) were generated and purified by cesium chloride ultracentrifugation. To investigate the profile of FNDC5/irisin expression in different types of cells, endothelial EA.hy926, muscle C2C12, hepatocytes Clone-9, and embryonic kidney HEK293 cells were employed for adenovirus gene delivery. By immunoblot analysis and enzyme-linked immunoassay (ELISA), it was found that Ad-irisin effectively transduced and conferred irisin secretion in all four types of cells whereas Ad-FNDC5 evoked moderate irisin secretion only in C2C12 and Clone-9 cells. Infection with Ad-irisin enhanced the viability and migration of endothelial cells, supporting the pro-angiogenic function of irisin. Besides, Ad-irisin-infected hepatocytes exhibited elevated activities of AMPK/Akt and inhibition of PEPCK signaling, suggesting the role of irisin in gluconeogenesis in the livers. With the development of these irisin-based tools, future studies are warranted to elucidate the cellular function of irisin in different organs, thereby exploring the therapeutic potential of irisin therapy for various human diseases. Advisors/Committee Members: Sheu, Jim Jinn-Chyuan (chair), Chen, Chun-Lin (chair), Tai, Ming-Hong (committee member).

Subjects/Keywords: angiogenesis; gene therapy; obesity; myokines; Irisin; gluconeogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shen, Y. (2017). Generation and Characterization of Recombinant Adenovirus Encoding Irisin. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0722117-235342

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shen, Ying-Ying. “Generation and Characterization of Recombinant Adenovirus Encoding Irisin.” 2017. Thesis, NSYSU. Accessed April 17, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0722117-235342.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shen, Ying-Ying. “Generation and Characterization of Recombinant Adenovirus Encoding Irisin.” 2017. Web. 17 Apr 2021.

Vancouver:

Shen Y. Generation and Characterization of Recombinant Adenovirus Encoding Irisin. [Internet] [Thesis]. NSYSU; 2017. [cited 2021 Apr 17]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0722117-235342.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shen Y. Generation and Characterization of Recombinant Adenovirus Encoding Irisin. [Thesis]. NSYSU; 2017. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0722117-235342

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Ottawa

2. Hutchinson, Kelly Ann. Assessing the Effect of Exercise During Pregnancy on Myokine Response and Placental Growth and Function In Vitro .

Degree: 2019, University of Ottawa

URL: http://hdl.handle.net/10393/39808

► Background: It is well established throughout the literature that regularly engaging in physical activity throughout pregnancy is associated with optimized health outcomes for both the… (more)

▼ Background: It is well established throughout the literature that regularly engaging in physical activity throughout pregnancy is associated with optimized health outcomes for both the mother and the fetus. The mediators and mechanistic pathways through which these observed exercise-induced outcomes are achieved are largely unknown. This thesis attempts to address this gap in knowledge. Methods: The objective of the first study was to develop an exercise protocol based on the recommendations from the ‘2019 Canadian guideline for physical activity throughout pregnancy’ and to subsequently evaluate the myokine response post-exercise. Pregnant (n=13) and non-pregnant (n=17) women performed a moderate-intensity bout of treadmill walking following which pre- and post-exercise serum for a panel of ten well-characterized myokines was analyzed. The objective of the second study was to evaluate whether acute and/or chronic exercise elicited changes in metrics of placental growth and development – thereby proposing possible mechanisms through which physical activity may be conferring health benefits to the fetus. Serum (pre- and post-exercise) collected from the first study was used to treat placental cell lines to assess the effect of acute exercise on cellular proliferation as well as nutrient transporter (GLUT1, SNAT1, FATP4) expression and localization. Term placental tissue collected from active (n=10) and non-active (n=10) participants in the PLACENTA study were used to evaluate the role of chronic exercise on changes in nutrient transporter (GLUT1, SNAT1, FATP4) expression and localization. Results: Pregnant women from the first study exhibited higher levels of four myokines post- versus pre-exercise: FGF21, EPO, BDNF and IL-15. As for the second study, BeWo cell lines treated with serum collected from pregnant women yielded higher GLUT1 expression compared to non-pregnant serum, independently of exercise. Lastly, FATP4 expression was found to be higher in term placentas of active compared to non-active pregnant women. Conclusion: This thesis identified four myokines that are elevated in the serum of pregnant women following a bout of acute exercise. The role of these myokines in pregnancy remains to be elucidated. Further, chronic and acute exercise are shown to alter expression of key placental macronutrient transporters.

Subjects/Keywords: Pregnancy; Physical Activity; Exercise; Myokines; Nutrient Transport

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APA (6^th Edition):

Hutchinson, K. A. (2019). Assessing the Effect of Exercise During Pregnancy on Myokine Response and Placental Growth and Function In Vitro . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/39808

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hutchinson, Kelly Ann. “Assessing the Effect of Exercise During Pregnancy on Myokine Response and Placental Growth and Function In Vitro .” 2019. Thesis, University of Ottawa. Accessed April 17, 2021. http://hdl.handle.net/10393/39808.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hutchinson, Kelly Ann. “Assessing the Effect of Exercise During Pregnancy on Myokine Response and Placental Growth and Function In Vitro .” 2019. Web. 17 Apr 2021.

Vancouver:

Hutchinson KA. Assessing the Effect of Exercise During Pregnancy on Myokine Response and Placental Growth and Function In Vitro . [Internet] [Thesis]. University of Ottawa; 2019. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10393/39808.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hutchinson KA. Assessing the Effect of Exercise During Pregnancy on Myokine Response and Placental Growth and Function In Vitro . [Thesis]. University of Ottawa; 2019. Available from: http://hdl.handle.net/10393/39808

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. van Gogh, IJA. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.

Degree: 2016, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/333972

► Skeletal muscle is a crucial organ in mediating (exercise-induced) beneficial health effects. In this thesis we gained important knowledge on the molecular biology of the… (more)

▼ Skeletal muscle is a crucial organ in mediating (exercise-induced) beneficial health effects. In this thesis we gained important knowledge on the molecular biology of the muscle. With our focus on the muscle, we investigated the crosstalk with other organs, the regulation of myokines and the role of nuclear receptors. First, we used an exercise mimic, electric pulse stimulation (EPS), to investigate the effect of the exercise-induced muscle secretome on the liver. We subjected C2C12 myotubes to EPS and hepatocytes were treated with this contraction-induced secretome. We demonstrate that EPS can induce both cell-mediated and non-cell-mediated effects on hepatocytes. Direct effects of EPS on C2C12 myotube function were mainly caused by EPS-induced contraction and not due to EPS-induced changes in cell culture media. This indicates that EPS clearly represents a valuable tool in exercise research, but care should be taken in experimental design to control for non-cell-mediated effects. Secondly, we assessed the importance of cellular context in Nur77-mediated gene regulation by comparing genome-wide DNA binding and gene expression profiles in C2C12 myotubes and RAW264.7 macrophages. These experiments revealed predominantly cell-type specific DNA binding of Nur77, with less than 16% of the Nur77 binding sites being shared between the two cell types. In addition, cell-type specific transcriptional regulation was observed, with genes differentially regulated in the same direction, in one cell-type only or even in an opposing manner. Newly identified Nur77 target genes include the genes encoding the myokines IL-15 and MCP-1. We suggest that besides Nur77 DNA binding itself, other mechanisms, including interplay with cell-specific factors, determine whether a potential Nur77 target gene is actually activated or repressed in a given cellular context. The third aim was to assess to what extent elevation of the myokine MCP-1 in muscle and elevated MCP-1 levels in plasma may be able to interfere with insulin signaling in skeletal muscle and cause insulin resistance. We made use of MCK-MCP-1 transgenic mice that specifically over-expresses MCP-1 in skeletal muscle. Our studies indicate that elevation of MCP-1 production in skeletal muscle and elevated MCP-1 levels in plasma promote inflammation in skeletal muscle but do not influence insulin signaling in skeletal muscle and have no effect on insulin sensitivity and glucose tolerance in lean and obese mice. Our data argue against MCP-1 promoting insulin resistance in skeletal muscle and raises questions about the impact of inflammation on insulin sensitivity in muscle. Last, we elucidated the impact of the first natural human LXRβ mutation on LXRβ function. By exome, sequencing, an alanine-to-threonine mutation in the LBD of LXRβ at the position 440 (LXRβ-A440T) was identified in a patient with several disorders (e.g. extremely fatty muscle). We demonstrate that this mutation results in a loss-of-function for classical LXRβ targets genes (Abcg1), while it also results in a… Advisors/Committee Members: Burgering, BMT, Kalkhoven, E.

Subjects/Keywords: Exercise; myokines; nuclear receptors; metabolism; skeletal muscle; Nur77; LXRβ; MCP-1

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APA (6^th Edition):

van Gogh, I. (2016). Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/333972

Chicago Manual of Style (16^th Edition):

van Gogh, IJA. “Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.” 2016. Doctoral Dissertation, Universiteit Utrecht. Accessed April 17, 2021. http://dspace.library.uu.nl:8080/handle/1874/333972.

MLA Handbook (7^th Edition):

van Gogh, IJA. “Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.” 2016. Web. 17 Apr 2021.

Vancouver:

van Gogh I. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2016. [cited 2021 Apr 17]. Available from: http://dspace.library.uu.nl:8080/handle/1874/333972.

Council of Science Editors:

van Gogh I. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. [Doctoral Dissertation]. Universiteit Utrecht; 2016. Available from: http://dspace.library.uu.nl:8080/handle/1874/333972

Boston University

4. Lopez, Timothy Magno. Evaluating the anti-proliferative effects of exercise on colorectal cancer cell lines HCT116 and HT29 through treatment of myokines produced ffrom C2C12 cells subjected to electric pulse stimulation.

Degree: MS, Medical Sciences, 2019, Boston University

URL: http://hdl.handle.net/2144/36594

► BACKGROUND: Colorectal cancer incidence and mortality rates are rising and are still one of the most common cancers worldwide. Its risks are associated with the… (more)

▼ BACKGROUND: Colorectal cancer incidence and mortality rates are rising and are still one of the most common cancers worldwide. Its risks are associated with the Western Lifestyle, important facets of this being increase physical inactivity and excess body weight. In sync with colorectal cancer’s increasing rates are obesity rates that are rising in both developed and developing countries. Obesity has been linked to several causes of death that includes cardiovascular disease and certain cancers. Studies have shown the benefits of exercise overtly in alleviating cardiovascular diseases but now have increasing evidence of its benefits in helping with cancer. Some studies have examined the effects of physical activity in colon cancer and have found a link between increase minutes of exercise weekly can slow cancer cell proliferation in colon crypts cells. Myokines are a newly discovered class of proteins that are produced by muscles and have multiple functions. One of those function is its anti-neoplastic activity against certain cancer cell types. Certain myokines evoke an anti-neoplastic effect on cancer, but there has not been an overwhelming agreement within the scientific community. OBJECTIVE: To investigate the anti-proliferative effects of exercise myokines produced by C2C12 cells in colorectal cancer cell lines: HCT116 and HT29, by looking at changes in protein expression through western blot analysis and protein arrays. METHODS: C2C12 cells were grown in cell culture plates and differentiated into myotubules. Myotubules were subjected to Electronic Pulse Stimulation using an apparatus called C-Pace by Ion Optix to generate myokines. Treat HCT116 and HT29 cell lines with exercise myokines and a control treatment and ultimately harvest their protein lysate for western blot analysis and protein array analysis. RESULTS: HCT116 treated with exercise myokines with different dilutions (1:25, 1:50, 1:100) a demonstrated significantly decreased proliferation (p<0.0001). HT29 treated with exercise myokines (1:25 dilution) also demonstrated a significant decrease in proliferation (p<0.0001). Western blot analysis of HCT116 treated with exercise myokines showed significantly lower expression in pRb (p<0.05), PCNA (p<0.05), and cyclin D1 (p<0.05). Western blot analysis of HT29 treated with exercise myokines revealed significant expression downregulation in exercise myokine treatment in PCNA (p<0.05), p42/p44 (p<0.05), pRb (p<0.0001) and Cyclin D1 (p<0.05). Human Phospho-Kinase Array demonstrated downregulation of the following proteins in HT29 cells treated with exercise myokines: GSK-3α/β, STAT3, EGFR, p53, PDGF Rβ, Src, PRAS40, WNK1, and JNK 1/2/3. Lastly, HT29 treated with exercise myokines showed downregulation of the p-EGFR and pHGFR as a result of the Human Phospho-RKT Array. CONCLUSION: Our data demonstrate that exercise myokines produced by Electric Pulse Stimulation of C2C12 cells have an anti-proliferative effect on colorectal cancer cell lines HCT116 and HT29. Further studies should be pursued to… Advisors/Committee Members: Chowdhury, Sanjib (advisor).

Subjects/Keywords: Cellular biology; C2C12; Colorectal cancer; Electric pulse stimulation; Exercise; Myokines; Obesity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lopez, T. M. (2019). Evaluating the anti-proliferative effects of exercise on colorectal cancer cell lines HCT116 and HT29 through treatment of myokines produced ffrom C2C12 cells subjected to electric pulse stimulation. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/36594

Chicago Manual of Style (16^th Edition):

Lopez, Timothy Magno. “Evaluating the anti-proliferative effects of exercise on colorectal cancer cell lines HCT116 and HT29 through treatment of myokines produced ffrom C2C12 cells subjected to electric pulse stimulation.” 2019. Masters Thesis, Boston University. Accessed April 17, 2021. http://hdl.handle.net/2144/36594.

MLA Handbook (7^th Edition):

Lopez, Timothy Magno. “Evaluating the anti-proliferative effects of exercise on colorectal cancer cell lines HCT116 and HT29 through treatment of myokines produced ffrom C2C12 cells subjected to electric pulse stimulation.” 2019. Web. 17 Apr 2021.

Vancouver:

Lopez TM. Evaluating the anti-proliferative effects of exercise on colorectal cancer cell lines HCT116 and HT29 through treatment of myokines produced ffrom C2C12 cells subjected to electric pulse stimulation. [Internet] [Masters thesis]. Boston University; 2019. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/2144/36594.

Council of Science Editors:

Lopez TM. Evaluating the anti-proliferative effects of exercise on colorectal cancer cell lines HCT116 and HT29 through treatment of myokines produced ffrom C2C12 cells subjected to electric pulse stimulation. [Masters Thesis]. Boston University; 2019. Available from: http://hdl.handle.net/2144/36594

5. Nadeau, Lucien. Investigating IL-15 Metabolic Impact and Its Mechanism of Action in Skeletal Muscle Cells .

Degree: 2017, University of Ottawa

URL: http://hdl.handle.net/10393/36054

► Skeletal muscle secretes many signalisation proteins named myokines. These myokines act as hormones and induce metabolic changes throughout the whole body to facilitate adaptation to… (more)

▼ Skeletal muscle secretes many signalisation proteins named myokines. These myokines act as hormones and induce metabolic changes throughout the whole body to facilitate adaptation to physical exercise. Interleukin-15 (IL-15) is highly expressed in skeletal muscle and appears to influence many metabolic parameters that are defective in metabolic pathologies such as insulin resistance. For instance, IL-15 increases glucose uptake in muscle and whole-body fatty acid oxidation and its overexpression in skeletal muscle in mice generates a very lean and active phenotype. However, there are discordant reports throughout scientific literature. The aim of the current study was to 1) characterize the metabolic effects of IL-15 in L6 myotubes to determine whether L6 is a good model to study IL-15 and 2) to determine whether IL-15 activates the AMPK signaling. L6 myotubes were exposed to different concentrations of IL-15 and different metabolic parameters were assayed namely; oxygen consumption, glucose uptake, fatty acid oxidation, Glucose transporter 4 (GLUT4) translocation, oxidative phosphorylation (OXPHOS) complexes protein expression, troponin T expression and Akt, AMPK and Acetyl-CoA Carboxylase (ACC) phosphorylation state. Acute IL-15 treatment increased glucose uptake without activating insulin signaling pathway or GLUT4 translocation. Furthermore, acute IL-15 treatment increased resting oxygen consumption rate (OCR) while chronic IL-15 treatment also increased mitochondrial spare capacity, suggesting an increased mitochondrial biogenesis. IL-15 induced ACC phosphorylation in a dose-dependent manner and tended to increase AMPK phosphorylation but it did not reach statistical significance. Lastly, IL-15 did not influence troponin T state. Altogether, the present study demonstrates that L6 myotubes do not express all the pro-oxidative qualities of IL-15 reported by scientific literature. Nonetheless, IL-15 induces certain pro-oxidative metabolic effect that could help people living with obesity and diabetes.

Subjects/Keywords: Metabolism; Myokines; IL-15; Muscle

…glycogen storage depletion and enhancing ATP production during ATP turnover. 5 1.2.3 Myokines… …from contracting muscle called myokines (Mathur and Pedersen 2008). Myokines can… …x28;Pedersen and Febbraio 2012). Myokines regroup multiple cytokines families. For… …remained undetermined. For instance, the most studied myokines, IL-6, acts both in an endocrine…

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APA (6^th Edition):

Nadeau, L. (2017). Investigating IL-15 Metabolic Impact and Its Mechanism of Action in Skeletal Muscle Cells . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/36054

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nadeau, Lucien. “Investigating IL-15 Metabolic Impact and Its Mechanism of Action in Skeletal Muscle Cells .” 2017. Thesis, University of Ottawa. Accessed April 17, 2021. http://hdl.handle.net/10393/36054.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nadeau, Lucien. “Investigating IL-15 Metabolic Impact and Its Mechanism of Action in Skeletal Muscle Cells .” 2017. Web. 17 Apr 2021.

Vancouver:

Nadeau L. Investigating IL-15 Metabolic Impact and Its Mechanism of Action in Skeletal Muscle Cells . [Internet] [Thesis]. University of Ottawa; 2017. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10393/36054.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nadeau L. Investigating IL-15 Metabolic Impact and Its Mechanism of Action in Skeletal Muscle Cells . [Thesis]. University of Ottawa; 2017. Available from: http://hdl.handle.net/10393/36054

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. Flores Opazo, Marcelo Alejandro. Exercise and adipose tissue GLUT4.

Degree: 2017, University of Melbourne

URL: http://hdl.handle.net/11343/192983

► GLUT4 is the major insulin-sensitive glucose transporter expressed predominantly in skeletal & cardiac muscles, and adipose tissue (AT) and mediates insulin-stimulated glucose transport into these… (more)

▼ GLUT4 is the major insulin-sensitive glucose transporter expressed predominantly in skeletal & cardiac muscles, and adipose tissue (AT) and mediates insulin-stimulated glucose transport into these tissues. Due to the major role of skeletal muscle in glucose disposal, considerable attention has focused on this tissue in order to understand how glucose homeostasis is affected by changes in muscle glucose metabolism. However, AT insulin-mediated glucose uptake and GLUT4 expression have been shown to be of importance for both glucose homeostasis and whole body insulin action. Interestingly, reduced GLUT4 expression in AT is a common defect found in insulin resistant states, including obesity, metabolic syndrome, and diabetes, whereas muscle GLUT4 expression is unaltered. Exercise increases AT-GLUT4 expression in rodents, and our lab has previously shown that 4 weeks of exercise training normalizes the expression of GLUT4 in the AT of patients with T2DM. However, the mechanisms involved in exercise-induced up-regulation of AT-GLUT4 are unknown. The broad aim of my research project was to examine the effect of exercise on AT-GLUT4 expression. With this purpose, we conducted three interventions using mice, human primary adipocytes and human subjects, in an attempt to gain a better understanding of: 1) how a high fat diet (HFD) affects the expression of AT-GLUT4, 2) how exercise may be beneficial to prevent this effect; and 3) how this effect may occur. Results showed that AT-GLUT4 protein is rapidly reduced by a HFD, suggesting this could be an early defect contributing to HFD-induced insulin resistance; exercise training increases GLUT4 protein in HFD-fed mice, short-term (10 d) exercise training did not affect GLUT4 levels in human, subcutaneous AT; and serum from exercised subjects increased GLUT4 protein and mRNA in human primary adipocytes suggesting that circulating factor(s) may mediate exercise effects on AT GLUT4 expression. Adipose tissue (AT) glucose transporter GLUT4 is reduced in insulin resistance (IR). Exercise training (EX) (4 weeks) normalized AT-GLUT4 expression in diabetic patients. However, mechanisms involved are unknown. Results showed: 1) AT-GLUT4 is reduced by high fat diet (HFD), which may contributes IR; 2) EX increased GLUT in HFD-fed mice, 3) short-term (10 d) EX didn’t affect GLUT4 in human AT; and 4) exercise serum increased GLUT4 in human primary adipocytes, suggesting circulating factor(s) may mediate EX-effects on AT GLUT4.

Subjects/Keywords: GLUT4; adipose tissue, exercise training; human primary adipocytes; high fat diet; adaptations to exercise; myokines

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APA (6^th Edition):

Flores Opazo, M. A. (2017). Exercise and adipose tissue GLUT4. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/192983

Chicago Manual of Style (16^th Edition):

Flores Opazo, Marcelo Alejandro. “Exercise and adipose tissue GLUT4.” 2017. Doctoral Dissertation, University of Melbourne. Accessed April 17, 2021. http://hdl.handle.net/11343/192983.

MLA Handbook (7^th Edition):

Flores Opazo, Marcelo Alejandro. “Exercise and adipose tissue GLUT4.” 2017. Web. 17 Apr 2021.

Vancouver:

Flores Opazo MA. Exercise and adipose tissue GLUT4. [Internet] [Doctoral dissertation]. University of Melbourne; 2017. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/11343/192983.

Council of Science Editors:

Flores Opazo MA. Exercise and adipose tissue GLUT4. [Doctoral Dissertation]. University of Melbourne; 2017. Available from: http://hdl.handle.net/11343/192983

7. Dubé, Chantal. The Effect of Exercise-induced Myokines on Placental Health and Function .

Degree: 2017, University of Ottawa

URL: http://hdl.handle.net/10393/36725

► Background: Exercise in pregnancy is associated with optimized fetal growth; however, the implicated mechanisms remain unknown. We hypothesize that exercise-induced myokines may be acting on… (more)

Subjects/Keywords: placenta; exercise; pregnancy; skeletal muscle; myokines

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APA (6^th Edition):

Dubé, C. (2017). The Effect of Exercise-induced Myokines on Placental Health and Function . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/36725

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dubé, Chantal. “The Effect of Exercise-induced Myokines on Placental Health and Function .” 2017. Thesis, University of Ottawa. Accessed April 17, 2021. http://hdl.handle.net/10393/36725.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dubé, Chantal. “The Effect of Exercise-induced Myokines on Placental Health and Function .” 2017. Web. 17 Apr 2021.

Vancouver:

Dubé C. The Effect of Exercise-induced Myokines on Placental Health and Function . [Internet] [Thesis]. University of Ottawa; 2017. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10393/36725.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dubé C. The Effect of Exercise-induced Myokines on Placental Health and Function . [Thesis]. University of Ottawa; 2017. Available from: http://hdl.handle.net/10393/36725

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

8. Nieuwoudt, Stephan. Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models.

Degree: PhD, Physiology and Biophysics, 2018, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227

► The beneficial effects of exercise for patients with type 2 diabetes (T2D) has been well established through critical advances in metabolic research. Two of the… (more)

▼ The beneficial effects of exercise for patients with type 2 diabetes (T2D) has been well established through critical advances in metabolic research. Two of the key benefits of exercise in T2D include improved insulin sensitivity and pancreatic ß-cell function, as defects in these systems primarily drive glucose intolerance in this patient population. The underlying mechanisms behind these benefits of exercise in T2D are still unknown, despite decades of intense investigation. First, this dissertation provides additional evidence that exercise, especially at a high intensity, can improve ß-cell function in adults with T2D. Myokine secretion from skeletal muscle may provide the mechanistic link between exercising skeletal muscle and the insulin secreting pancreatic ß-cell. Determining this direct cross-talk effect required the development of an “exercise in a petri dish” system, enabling the isolation of the systemic effects of exercise and muscle contraction alone. Details are provided for the development of a successful in vitro contraction system using C2C12 myotubes, along with design information for the construction of a platinum wire electrode system. First, the model had to be validated against a complicated exercise-mediated phenomenon. The accumulation of excess saturated lipid in plasma has been implicated in both the development of insulin resistance and T2D, with prior exercise protecting against lipid-induced insulin resistance. In vitro contraction of muscle cells via electrical stimulation is shown here to effectively protect against lipid-induced insulin resistance, evident at the levels of glucose uptake and proximal insulin signaling. With a validated model in hand, the crosstalk of contracting muscle and ß-cells (MIN6) was evaluated. Secretory products from contracted C2C12 myotubes were able to enhance MIN6 glucose stimulated insulin secretion, providing experimental support for exercise-mediated crosstalk. These data establish the central role of muscle contraction in driving improved insulin sensitivity and ß-cell function in T2D. Advisors/Committee Members: Kirwan, John (Advisor), Dubyak, George (Committee Chair).

Subjects/Keywords: Physiology; Biophysics; Biomedical Research; Molecular Biology; Type 2 Diabetes; Exercise; Skeletal Muscle; In Vitro; Myokines; Insulin Resistance; Beta Cell Function

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APA (6^th Edition):

Nieuwoudt, S. (2018). Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227

Chicago Manual of Style (16^th Edition):

Nieuwoudt, Stephan. “Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models.” 2018. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed April 17, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227.

MLA Handbook (7^th Edition):

Nieuwoudt, Stephan. “Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models.” 2018. Web. 17 Apr 2021.

Vancouver:

Nieuwoudt S. Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2018. [cited 2021 Apr 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227.

Council of Science Editors:

Nieuwoudt S. Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2018. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227

9. Segsworth, Blair M. Acute Sprint Interval Exercise Induces a Greater FGF-21 Response in Comparison to Work-Matched Continuous Exercise.

Degree: 2015, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/3254

► Sprint interval training (SIT) has been associated with substantial reductions in body fat. Recent evidence suggests that myokines (small protein compounds produced in muscle) may… (more)

Subjects/Keywords: Irisin; Fibroblast Growth Factor-21; Interleukin-15; Myokines; fat loss

…Febbraio, 2013). These have become known as myokines because the tissue of origin for these… …cytokines is muscle and, as of 2014, there are at least 69 identified myokines within the… …secretome of muscle (Catoire et al., 2014). One of the most well characterized myokines… …new subgroup of myokines has been identified as perhaps playing a role in how exercise… …x28;IL-15) are three novel myokines that have been implicated with fat metabolism…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Segsworth, B. M. (2015). Acute Sprint Interval Exercise Induces a Greater FGF-21 Response in Comparison to Work-Matched Continuous Exercise. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/3254

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Segsworth, Blair M. “Acute Sprint Interval Exercise Induces a Greater FGF-21 Response in Comparison to Work-Matched Continuous Exercise.” 2015. Thesis, University of Western Ontario. Accessed April 17, 2021. https://ir.lib.uwo.ca/etd/3254.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Segsworth, Blair M. “Acute Sprint Interval Exercise Induces a Greater FGF-21 Response in Comparison to Work-Matched Continuous Exercise.” 2015. Web. 17 Apr 2021.

Vancouver:

Segsworth BM. Acute Sprint Interval Exercise Induces a Greater FGF-21 Response in Comparison to Work-Matched Continuous Exercise. [Internet] [Thesis]. University of Western Ontario; 2015. [cited 2021 Apr 17]. Available from: https://ir.lib.uwo.ca/etd/3254.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Segsworth BM. Acute Sprint Interval Exercise Induces a Greater FGF-21 Response in Comparison to Work-Matched Continuous Exercise. [Thesis]. University of Western Ontario; 2015. Available from: https://ir.lib.uwo.ca/etd/3254

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. HARNISH, CHRISTOPHER R. Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute Metabolic and Inflammatory Responses.

Degree: PhD, Rehabilitation and Movement Science, 2014, Virginia Commonwealth University

URL: https://doi.org/10.25772/XFBM-WA70 ; https://scholarscompass.vcu.edu/etd/3565

► High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only… (more)

Subjects/Keywords: SIT; Cytokines; Myokines; Insulin Sensitivity; Wingate; Tabata; OGTT; Cardiovascular Diseases; Cellular and Molecular Physiology; Exercise Physiology; Exercise Science; Kinesiology; Medical Immunology; Medical Physiology; Physiological Processes; Sports Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

HARNISH, C. R. (2014). Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute Metabolic and Inflammatory Responses. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/XFBM-WA70 ; https://scholarscompass.vcu.edu/etd/3565

Chicago Manual of Style (16^th Edition):

HARNISH, CHRISTOPHER R. “Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute Metabolic and Inflammatory Responses.” 2014. Doctoral Dissertation, Virginia Commonwealth University. Accessed April 17, 2021. https://doi.org/10.25772/XFBM-WA70 ; https://scholarscompass.vcu.edu/etd/3565.

MLA Handbook (7^th Edition):

HARNISH, CHRISTOPHER R. “Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute Metabolic and Inflammatory Responses.” 2014. Web. 17 Apr 2021.

Vancouver:

HARNISH CR. Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute Metabolic and Inflammatory Responses. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2014. [cited 2021 Apr 17]. Available from: https://doi.org/10.25772/XFBM-WA70 ; https://scholarscompass.vcu.edu/etd/3565.

Council of Science Editors:

HARNISH CR. Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute Metabolic and Inflammatory Responses. [Doctoral Dissertation]. Virginia Commonwealth University; 2014. Available from: https://doi.org/10.25772/XFBM-WA70 ; https://scholarscompass.vcu.edu/etd/3565

11. van Gogh, IJA. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.

Degree: 2016, University Utrecht

URL: http://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; http://dspace.library.uu.nl/handle/1874/333972

► Skeletal muscle is a crucial organ in mediating (exercise-induced) beneficial health effects. In this thesis we gained important knowledge on the molecular biology of the… (more)

▼ Skeletal muscle is a crucial organ in mediating (exercise-induced) beneficial health effects. In this thesis we gained important knowledge on the molecular biology of the muscle. With our focus on the muscle, we investigated the crosstalk with other organs, the regulation of myokines and the role of nuclear receptors. First, we used an exercise mimic, electric pulse stimulation (EPS), to investigate the effect of the exercise-induced muscle secretome on the liver. We subjected C2C12 myotubes to EPS and hepatocytes were treated with this contraction-induced secretome. We demonstrate that EPS can induce both cell-mediated and non-cell-mediated effects on hepatocytes. Direct effects of EPS on C2C12 myotube function were mainly caused by EPS-induced contraction and not due to EPS-induced changes in cell culture media. This indicates that EPS clearly represents a valuable tool in exercise research, but care should be taken in experimental design to control for non-cell-mediated effects. Secondly, we assessed the importance of cellular context in Nur77-mediated gene regulation by comparing genome-wide DNA binding and gene expression profiles in C2C12 myotubes and RAW264.7 macrophages. These experiments revealed predominantly cell-type specific DNA binding of Nur77, with less than 16% of the Nur77 binding sites being shared between the two cell types. In addition, cell-type specific transcriptional regulation was observed, with genes differentially regulated in the same direction, in one cell-type only or even in an opposing manner. Newly identified Nur77 target genes include the genes encoding the myokines IL-15 and MCP-1. We suggest that besides Nur77 DNA binding itself, other mechanisms, including interplay with cell-specific factors, determine whether a potential Nur77 target gene is actually activated or repressed in a given cellular context. The third aim was to assess to what extent elevation of the myokine MCP-1 in muscle and elevated MCP-1 levels in plasma may be able to interfere with insulin signaling in skeletal muscle and cause insulin resistance. We made use of MCK-MCP-1 transgenic mice that specifically over-expresses MCP-1 in skeletal muscle. Our studies indicate that elevation of MCP-1 production in skeletal muscle and elevated MCP-1 levels in plasma promote inflammation in skeletal muscle but do not influence insulin signaling in skeletal muscle and have no effect on insulin sensitivity and glucose tolerance in lean and obese mice. Our data argue against MCP-1 promoting insulin resistance in skeletal muscle and raises questions about the impact of inflammation on insulin sensitivity in muscle. Last, we elucidated the impact of the first natural human LXRβ mutation on LXRβ function. By exome, sequencing, an alanine-to-threonine mutation in the LBD of LXRβ at the position 440 (LXRβ-A440T) was identified in a patient with several disorders (e.g. extremely fatty muscle). We demonstrate that this mutation results in a loss-of-function for classical LXRβ targets genes (Abcg1), while it also results in a… Advisors/Committee Members: Burgering, BMT, Kalkhoven, E.

Subjects/Keywords: Exercise; myokines; nuclear receptors; metabolism; skeletal muscle; Nur77; LXRβ; MCP-1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

van Gogh, I. (2016). Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. (Doctoral Dissertation). University Utrecht. Retrieved from http://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; http://dspace.library.uu.nl/handle/1874/333972

Chicago Manual of Style (16^th Edition):

van Gogh, IJA. “Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.” 2016. Doctoral Dissertation, University Utrecht. Accessed April 17, 2021. http://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; http://dspace.library.uu.nl/handle/1874/333972.

MLA Handbook (7^th Edition):

van Gogh, IJA. “Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.” 2016. Web. 17 Apr 2021.

Vancouver:

van Gogh I. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. [Internet] [Doctoral dissertation]. University Utrecht; 2016. [cited 2021 Apr 17]. Available from: http://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; http://dspace.library.uu.nl/handle/1874/333972.

Council of Science Editors:

van Gogh I. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. [Doctoral Dissertation]. University Utrecht; 2016. Available from: http://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; http://dspace.library.uu.nl/handle/1874/333972

12. van Gogh, IJA. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.

Degree: 2016, University Utrecht

URL: https://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; https://dspace.library.uu.nl/handle/1874/333972

► Skeletal muscle is a crucial organ in mediating (exercise-induced) beneficial health effects. In this thesis we gained important knowledge on the molecular biology of the… (more)

▼ Skeletal muscle is a crucial organ in mediating (exercise-induced) beneficial health effects. In this thesis we gained important knowledge on the molecular biology of the muscle. With our focus on the muscle, we investigated the crosstalk with other organs, the regulation of myokines and the role of nuclear receptors. First, we used an exercise mimic, electric pulse stimulation (EPS), to investigate the effect of the exercise-induced muscle secretome on the liver. We subjected C2C12 myotubes to EPS and hepatocytes were treated with this contraction-induced secretome. We demonstrate that EPS can induce both cell-mediated and non-cell-mediated effects on hepatocytes. Direct effects of EPS on C2C12 myotube function were mainly caused by EPS-induced contraction and not due to EPS-induced changes in cell culture media. This indicates that EPS clearly represents a valuable tool in exercise research, but care should be taken in experimental design to control for non-cell-mediated effects. Secondly, we assessed the importance of cellular context in Nur77-mediated gene regulation by comparing genome-wide DNA binding and gene expression profiles in C2C12 myotubes and RAW264.7 macrophages. These experiments revealed predominantly cell-type specific DNA binding of Nur77, with less than 16% of the Nur77 binding sites being shared between the two cell types. In addition, cell-type specific transcriptional regulation was observed, with genes differentially regulated in the same direction, in one cell-type only or even in an opposing manner. Newly identified Nur77 target genes include the genes encoding the myokines IL-15 and MCP-1. We suggest that besides Nur77 DNA binding itself, other mechanisms, including interplay with cell-specific factors, determine whether a potential Nur77 target gene is actually activated or repressed in a given cellular context. The third aim was to assess to what extent elevation of the myokine MCP-1 in muscle and elevated MCP-1 levels in plasma may be able to interfere with insulin signaling in skeletal muscle and cause insulin resistance. We made use of MCK-MCP-1 transgenic mice that specifically over-expresses MCP-1 in skeletal muscle. Our studies indicate that elevation of MCP-1 production in skeletal muscle and elevated MCP-1 levels in plasma promote inflammation in skeletal muscle but do not influence insulin signaling in skeletal muscle and have no effect on insulin sensitivity and glucose tolerance in lean and obese mice. Our data argue against MCP-1 promoting insulin resistance in skeletal muscle and raises questions about the impact of inflammation on insulin sensitivity in muscle. Last, we elucidated the impact of the first natural human LXRβ mutation on LXRβ function. By exome, sequencing, an alanine-to-threonine mutation in the LBD of LXRβ at the position 440 (LXRβ-A440T) was identified in a patient with several disorders (e.g. extremely fatty muscle). We demonstrate that this mutation results in a loss-of-function for classical LXRβ targets genes (Abcg1), while it also results in a… Advisors/Committee Members: Burgering, BMT, Kalkhoven, E.

Subjects/Keywords: Exercise; myokines; nuclear receptors; metabolism; skeletal muscle; Nur77; LXRβ; MCP-1

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

van Gogh, I. (2016). Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; https://dspace.library.uu.nl/handle/1874/333972

Chicago Manual of Style (16^th Edition):

van Gogh, IJA. “Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.” 2016. Doctoral Dissertation, University Utrecht. Accessed April 17, 2021. https://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; https://dspace.library.uu.nl/handle/1874/333972.

MLA Handbook (7^th Edition):

van Gogh, IJA. “Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism.” 2016. Web. 17 Apr 2021.

Vancouver:

van Gogh I. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. [Internet] [Doctoral dissertation]. University Utrecht; 2016. [cited 2021 Apr 17]. Available from: https://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; https://dspace.library.uu.nl/handle/1874/333972.

Council of Science Editors:

van Gogh I. Nuclear receptors and myokines : mediators of exercise-induced skeletal muscle metabolism. [Doctoral Dissertation]. University Utrecht; 2016. Available from: https://dspace.library.uu.nl/handle/1874/333972 ; URN:NBN:NL:UI:10-1874-333972 ; urn:isbn:978-90-393-6564-9 ; URN:NBN:NL:UI:10-1874-333972 ; https://dspace.library.uu.nl/handle/1874/333972

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Open Access Theses and Dissertations