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

J Hepatol. 2008 Dec;49(6):1019-28. doi: 10.1016/j.jhep.2008.08.012. Epub 2008 Oct 7.

Abstract

Background/aims: Resveratrol, a polyphenolic activator of the silent information regulation 2 homolog 1 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Body Weight
  • Diet, Atherogenic*
  • Eating
  • Fatty Liver / drug therapy*
  • Fatty Liver / pathology
  • Fatty Liver / physiopathology
  • Gene Expression / drug effects
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Lipids / blood
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Organ Size
  • Resveratrol
  • Stilbenes / pharmacology*

Substances

  • Antioxidants
  • Lipids
  • Stilbenes
  • Resveratrol