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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Mueller, M; Thorell, A; Claudel, T; Jha, P; Koefeler, H; Lackner, C; Hoesel, B; Fauler, G; Stojakovic, T; Einarsson, C; Marschall, HU; Trauner, M.
Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity.
J Hepatol. 2015; 62(6):1398-1404 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Claudel Thierry
Fauler Günter
Jha Pooja
Köfeler Harald
Lackner Karoline
Müller Michaela
Stojakovic Tatjana
Trauner Michael
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Abstract:
Bile acids (BAs) are major regulators of hepatic BA and lipid metabolism but their mechanisms of action in non-alcoholic fatty liver disease (NAFLD) are still poorly understood. Here we aimed to explore the molecular and biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross-talk between liver and visceral white adipose tissue (vWAT) regarding BA and cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD patients. In this randomized controlled pharmacodynamic study, we analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese patients receiving UDCA (20 mg/kg/day) or no treatment three weeks prior to bariatric surgery. Short term UDCA administration stimulated BA synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X receptor (FXR) activation, resulting in cholesterol 7α-hydroxylase induction mirrored by elevated C4 and 7α-hydroxycholesterol. Enhanced BA formation depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the liver, thereby increasing hepatic triglyceride content. In addition, induced SCD activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic and more lipogenic monounsaturated fatty acids such as oleic acid. These data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces neutral lipid accumulation in both liver and vWAT. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Bile Acids and Salts - biosynthesis
Bile Acids and Salts - metabolism
Humans -
Intra-Abdominal Fat - drug effects
Intra-Abdominal Fat - metabolism
Lipid Metabolism - drug effects
Liver - drug effects
Liver - metabolism
Non-alcoholic Fatty Liver Disease - drug therapy
Non-alcoholic Fatty Liver Disease - metabolism
Obesity, Morbid - drug therapy
Obesity, Morbid - metabolism
Oleic Acid - metabolism
Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors
Stearoyl-CoA Desaturase - biosynthesis
Ursodeoxycholic Acid - administration & dosage
Ursodeoxycholic Acid - pharmacology

Find related publications in this database (Keywords)
Non-alcoholic fatty liver disease
FGF19
3-hydroxy-3-methylglutaryl-CoA reductase
Lipogenesis
Stearoyl-CoA desaturase
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