Research Article Details
Article ID: | A26226 |
PMID: | 20868235 |
Source: | Biol Chem |
Title: | Bile acid retention and activation of endogenous hepatic farnesoid-X-receptor in the pathogenesis of fatty liver disease in ob/ob-mice. |
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. |
DOI: | 10.1515/BC.2010.141 |

Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
---|---|---|---|---|---|
S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
---|---|---|---|---|---|---|---|
T17 | Farnesoid X-activated receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
Diseases ID | DO ID | Disease Name | Definition | Class | |
---|---|---|---|---|---|
I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |