Bile acid retention and activation of endogenous hepatic farnesoid-X-receptor in the pathogenesis of fatty liver disease in ob/ob-mice
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Ina V. Martin
Abstract
The nuclear bile acid receptor FXR (farnesoid-X-receptor) has recently been implicated in the pathophysiology of non-alcoholic fatty liver disease because selective FXR-agonists improve glucose and lipid metabolism in rodent models of obesity. However, the regulation of FXR and other relevant nuclear receptors as well as their lipogenic target genes in fatty liver is still not revealed in detail. Livers were harvested from 14-week-old male ob/ob mice and wild-type controls. Serum bile acids were quantified by radioimmunoassay. mRNA and protein expression of transporters and nuclear receptors was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting, whereas DNA binding to the IR-1 element was examined by electrophoretic mobility shift assay. In this study we show: (i) bile acid retention in ob/ob mice, (ii) a resulting FXR upregulation and binding to the IR-1 element in ob/ob animals and (iii) concomitant activation of the fatty acid synthase as a potential lipogenic FXR target gene in vivo. The present study suggests a potential role of hepatic bile acid retention and FXR activation in the induction of lipogenic target genes. Differences between intestinal and hepatic FXR could explain apparent contradictory information regarding its effects on fatty liver disease.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Minireview
- Physiology and pathophysiology of the RANKL/RANK system
- Genes and Nucleic Acids
- Murine aldo-keto reductase family 1 subfamily B: identification of AKR1B8 as an ortholog of human AKR1B10
- Characterization of plant miRNAs and small RNAs derived from potato spindle tuber viroid (PSTVd) in infected tomato
- Protein Structure and Function
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- Secretion of hepatoma-derived growth factor is regulated by N-terminal processing
- Twin arginine translocation (Tat)-dependent protein transport: the passenger protein participates in the initial membrane binding step
- Kinetic and structural characterization of bacterial glutaminyl cyclases from Zymomonas mobilis and Myxococcus xanthus
- Membranes, Lipids, Glycobiology
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- Molecular Medicine
- Bile acid retention and activation of endogenous hepatic farnesoid-X-receptor in the pathogenesis of fatty liver disease in ob/ob-mice
- Cell Biology and Signaling
- Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal β-cells
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- Increase of SARS-CoV 3CL peptidase activity due to macromolecular crowding effects in the milieu composition
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- Acknowledgement
- Acknowledgement
