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Ursodeoxycholic acid decreases age-related adipocity and inflammation in mice
Ah-Reum Oh1,#, Jin-Sik Bae1,#, Junghoon Lee1, Eunji Shin1, Byeong-Chul Oh1, Sang-Chul Park1, Ji-Young Cha1,2,*
1Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University,
2Gachon Medical Research Institute, Gil Hospital
Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic influence of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-ャ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli.
Abstract, Accepted Manuscript(in press) [Submitted on August 17, 2015, Accepted on September 2, 2015]
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