Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet

Background/Aims: Resveratrol, a polyphenolic activator of the silent information regulation 2 homolog I (SIRT1), is known to extend lifespan and improve metabolic disease. The aim of the present study is to test whether resveratrol protects against metabolic steatohepatitis through the modulation of lipid metabolism-related genes. Methods: We used a mouse model in which steatohepatitis can be induced by an atherogenic diet (Ath diet) to evaluate the effects of resveratrol on steatotic hepatitis and hepatic gene expression. Results: The Ath diet induced excessive weight gain, hepatomegaly, dyslipidemia, and steatohepatitis after 8 weeks. The addition of resveratrol protected against Ath diet-induced changes and also alleviated steatohepatitis. Whole-genome expression analysis revealed that an Ath diet altered the hepatic expression of genes involved in lipid metabolism, and the addition of resveratrol to the diet reversed that effect. Real-time PCR and Western blot analysis confirmed the Ath diet up-regulated the levels of genes related to lipogenesis and down-regulated genes involved in lipolysis. Resveratrol clearly suppressed the Ath diet-induced alterations of the expression of genes related to lipid metabolism. Conclusions: Resveratrol ameliorated dyslipidemia and steatohepatitis induced by the Ath diet, and its beneficial effects were associated with the altered expression of hepatic genes involved in lipid metabolism. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.