Resveratrol alleviates alcoholic fatty liver in mice
Am J Physiol Gastrointest Liver Physiol 295: G833-G842, 2008
Alcoholic fatty liver is associated with inhibition of sirtuin
1 (SIRT1) and AMP-activated kinase (AMPK), two critical signaling
molecules regulating the pathways of hepatic lipid metabolism
in animals. Resveratrol, a dietary polyphenol, has been identified
as a potent activator for both SIRT1 and AMPK.
In the present
study, we have carried out in vivo animal experiments that test
the ability of resveratrol to reverse the inhibitory effects
of chronic ethanol feeding on hepatic SIRT1-AMPK signaling system
and to prevent the development of alcoholic liver steatosis.
Resveratrol treatment increased SIRT1 expression levels and
stimulated AMPK activity in livers of ethanol-fed mice. The
resveratrol-mediated increase in activities of SIRT1 and AMPK
was associated with suppression of sterol regulatory element
binding protein 1 (SREBP-1) and activation of peroxisome proliferator-activated
receptor
coactivator
(PGC-1
). In parallel, in ethanol-fed
mice, resveratrol administration markedly increased circulating
adiponectin levels and enhanced mRNA expression of hepatic adiponectin
receptors (AdipoR1/R2).
In conclusion, resveratrol treatment
led to reduced lipid synthesis and increased rates of fatty
acid oxidation and prevented alcoholic liver steatosis. The
protective action of resveratrol is in whole or in part mediated
through the upregulation of a SIRT1-AMPK signaling system in
the livers of ethanol-fed mice.
Our study suggests that resveratrol
may serve as a promising agent for preventing or treating human
alcoholic fatty liver disease.
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