title: Coumarin attenuates hepatic steatosis by down-regulating lipogenic gene expression in mice fed a high-fat diet.
abstract: Coumarin is a natural compound abundant in plant-based foods such as citrus fruits, tomatoes, vegetables and green tea. Although coumarin has been reported to exhibit anti-coagulant, anti-inflammation and cholesterol-lowering properties, the effect of coumarin on hepatic lipid metabolism remains unclear. In the present study, we evaluated the ability of coumarin to protect against hepatic steatosis associated with a high-fat diet (HFD) and investigated potential mechanisms underlying this effect. C57BL/6J mice were fed a normal diet, HFD and HFD containing 0·05 % courmarin for 8 weeks. The present results showed that coumarin reduced weight gain and abdominal fat mass in mice fed the HFD for 8 weeks (P< 0·05). Coumarin also significantly reduced the HFD-induced elevation in total cholesterol, apoB, leptin and insulin (P< 0·05). In the liver of HFD-fed mice, coumarin significantly reduced total lipids, TAG and cholesterol (38, 22 and 9 % reductions, respectively; P< 0·05), as well as lipid droplet number and size. Additionally, thiobarbituric acid-reactive substance levels, as an indicator of hepatic steatosis, were attenuated by coumarin (P< 0·05). Finally, coumarin suppressed the HFD-induced up-regulation in fatty acid synthase (FAS) activity, and the expression of sterol regulatory element-binding protein-1, FAS, acetyl-CoA carboxylase 1, PPARγ and CCAAT/enhancer-binding protein-α in the liver. Taken together, these results demonstrate that coumarin could prevent HFD-induced hepatic steatosis by regulating lipogenic gene expression, suggesting potential targets for preventing hepatic steatosis.
authors.affiliation: Division of Metabolism and Functionality Research, Korea Food Research Institute, 516 Baekhyun-Dong, Bundang-Gu, Sungnam, Republic of Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Um
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Moon
authors.forename: Jiyun
authors.initials: J
authors.lastname: Ahn
authors.forename: Tae
authors.initials: T
authors.lastname: Youl Ha
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D017931:DNA Primers; D004041:Dietary Fats / Q000008:administration & dosage*; D015536:Down-Regulation; D005234:Fatty Liver / Q000517:prevention & control*; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances
chemical_list: D003374:Coumarins; D017931:DNA Primers; D004041:Dietary Fats; D017392:Thiobarbituric Acid Reactive Substances; C030123:coumarin