Journal
JOURNAL OF LIPID RESEARCH
Volume 51, Issue 12, Pages 3414-3424Publisher
ELSEVIER
DOI: 10.1194/jlr.M007179
Keywords
nonalcoholic fatty liver disease; tumor necrosis factor alpha; occludin; endotoxin
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Funding
- German Ministry of Education and Science (BMBF) [03105084]
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Fructose intake is being discussed as a key dietary factor in the development of nonalcoholic fatty liver disease (NAFLD). Bile acids have been shown to modulate energy metabolism. We tested the effects of bile acids on fructose-induced hepatic steatosis. In C57BL/6J mice treated with a combination of chenodeoxycholic acid and cholic acid (100 mg/kg body weight each) while drinking water or a 30% fructose solution for eight weeks and appropriate controls, markers of hepatic steatosis, portal endotoxin levels, and markers of hepatic lipogenesis were determined. In mice concomitantly treated with bile acids, the onset of fructose-induced hepatic steatosis was markedly attenuated compared to mice only fed fructose. The protective effects of the bile acid treatment were associated with a downregulation of tumor necrosis factor (TNF) alpha, sterol regulatory element-binding protein (SREBP) 1, FAS mRNA expression, and lipid peroxidation in the liver, whereas hepatic farnesoid X receptor (FXR) or short heterodimer partner (SHP) protein concentration did not differ between groups fed fructose. Rather, bile acid treatment normalized occludin protein concentration in the duodenum, portal endotoxin levels, and markers of Kupffer cell activation to the level of water controls.jlr Taken together, these data suggest that bile acids prevent fructose-induced hepatic steatosis in mice through mechanisms involving protection against the fructose-induced translocation of intestinal bacterial endotoxin.-Volynets, V., A. Spruss, G. Kanuri, S. Wagnerberger, S. C. Bischoff, and I. Bergheim. Protective effect of bile acids on the onset of fructose-induced hepatic steatosis in mice. J. Lipid Res. 51: 3414-3424.
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