Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice.
Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects 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-γ, 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 the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli. [BMB Reports 2016; 49(2): 105-110].
Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.
Ah-Reum
AR
Oh
Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.
Jin-Sik
JS
Bae
Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.
Junghoon
J
Lee
Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.
Eunji
E
Shin
Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.
Byung-Chul
BC
Oh
Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.
Sang-Chul
SC
Park
Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999; Gachon Medical Research Institute, Gil Hospital, Incheon 21565, Korea.
Ji-Young
JY
Cha
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D050154:Adiposity / Q000187:drug effects*; D000375:Aging / Q000097:blood / Q000187:drug effects* / Q000473:pathology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D007249:Inflammation / Q000097:blood / Q000473:pathology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D014158:Transcription, Genetic / Q000187:drug effects; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D014580:Ursodeoxycholic Acid