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University of Oulu

1. Käräjämäki, A. (Aki). Non-alcoholic fatty liver disease (NAFLD):perspectives to etiology, complications and lipid metabolism.

Degree: 2017, University of Oulu

Abstract Obesity, insulin resistance, type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) form a dangerous quartet which threatens human health all over the world. About 25% of adults around the world have NAFLD, which poses risks for cardiovascular and metabolic well-being and may develop into liver cirrhosis and hepatocellular carcinoma. Apart from lifestyle modification, treatment options for NAFLD are scarce. This thesis presents atrial fibrillation (AF) as a new complication of NAFLD among general population of 958 individuals aged 40-60 years participating in the OPERA study. Even after multiple-adjustments for confounding factors, ultrasound-based NAFLD predicted the development of AF during about 16 years of follow-up. Moreover, the association between AF and liver fibrosis in 76 individuals aged 64-82 years in a cross-sectional setting is presented. The thesis also shows that individuals with metabolic syndrome (MetS), with or without NAFLD, are at increased risk of cardiovascular events, T2D and the increase of left ventricular mass index in a study population of 958 individuals aged 40-60 years during a 20-year follow-up. In other words, NAFLD without MetS does not seem to expose to these three cardiometabolic complications. The thesis also shows that rifampicin-activated pregnane X receptor (PXR), a member of the nuclear receptor superfamily of ligand-activated transcription factors with several endobiotic and xenobiotic activators, increases serum levels of cholesterol, phospholipids and certain fatty acids, assessed by nuclear magnetic resonance metabolomics technique, in a randomized, open, placebo-controlled trial among 34 young and healthy individuals. These serum lipids are considered toxic lipids and capable of transforming hepatosteatosis into steatohepatitis and even more severe forms of NAFLD. Moreover, rifampicin-activated PXR has no effect on serum triglycerides, that are non-toxic lipids, or triglyceride accumulation in the liver, assessed by magnetic resonance imaging, in 15 young and healthy individuals. In conclusion, this thesis advances the knowledge in the pathogenesis, lipid metabolism, complications and heterogeneous nature of NAFLD. These may have implications for patient care and follow-up.

Tiivistelmä Maailmanlaajuisesti noin 25% täysi-ikäisistä henkilöistä sairastaa alkoholinkäyttöön liittymätöntä rasvamaksaa. Sen tiedetään altistavan sydän- ja verisuonisairauksille, aineenvaihduntahäiriöille, maksakirroosille ja jopa maksasyövälle, mutta elämäntapahoitoa lukuun ottamatta hoitomahdollisuudet ovat toistaiseksi vähäisiä. Tässä väitöskirjassa osoitetaan ensimmäistä kertaa alkoholinkäyttöön liittymättömän rasvamaksan ennustavan itsenäisesti eteisvärinän ilmaantuvuutta noin 16 vuoden seurannan aikana 958 tavallisen keski-ikäisen ihmisen aineistossa osana OPERA-tutkimusta. Lisäksi väitöskirjassa osoitetaan maksan sidekudosmuodostuksen ja eteisvärinän välillä olevan yhteys poikkileikkausasetelmassa 76 iäkkään ihmisen muodostamassa aineistossa. Väitöstutkimuksessa…

Advisors/Committee Members: Ukkola, O. (Olavi), Hukkanen, J. (Janne).

Subjects/Keywords: atrial fibrillation; cardiovascular diseases; liver fibrosis; non-alcoholic fatty liver disease; pregnane X receptor; type 2 diabetes; alkoholin käyttöön liittymätön rasvamaksa; eteisvärinä; maksafibroosi; pregnaani X reseptori; sydän- ja verisuonisairaudet; tyypin 2 diabetes

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

APA (6th Edition):

Käräjämäki, A. (. (2017). Non-alcoholic fatty liver disease (NAFLD):perspectives to etiology, complications and lipid metabolism. (Doctoral Dissertation). University of Oulu. Retrieved from http://urn.fi/urn:isbn:9789526217376

Chicago Manual of Style (16th Edition):

Käräjämäki, A (Aki). “Non-alcoholic fatty liver disease (NAFLD):perspectives to etiology, complications and lipid metabolism.” 2017. Doctoral Dissertation, University of Oulu. Accessed January 21, 2021. http://urn.fi/urn:isbn:9789526217376.

MLA Handbook (7th Edition):

Käräjämäki, A (Aki). “Non-alcoholic fatty liver disease (NAFLD):perspectives to etiology, complications and lipid metabolism.” 2017. Web. 21 Jan 2021.

Vancouver:

Käräjämäki A(. Non-alcoholic fatty liver disease (NAFLD):perspectives to etiology, complications and lipid metabolism. [Internet] [Doctoral dissertation]. University of Oulu; 2017. [cited 2021 Jan 21]. Available from: http://urn.fi/urn:isbn:9789526217376.

Council of Science Editors:

Käräjämäki A(. Non-alcoholic fatty liver disease (NAFLD):perspectives to etiology, complications and lipid metabolism. [Doctoral Dissertation]. University of Oulu; 2017. Available from: http://urn.fi/urn:isbn:9789526217376

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