Resveratrol protects against hepatic insulin resistance in a rat's model of non-alcoholic fatty liver disease by down-regulation of GPAT-1 and DGAT2 expression and inhibition of PKC membranous translocation.

Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance (IR). Resveratrol (RES) a potent hypolipidemic dietary polyphenol has been identified for its ability to prevent hepatic steatosis and hepatic IR in high-fat diet (HFD)-fed murine models of NAFLD. In the present study, we have carried an in vivo animal experiment to identify a novel mechanism for RES protective action. Sub-chronic (45 days) RES pre-treatment in 3 days HFD-fed adult Wistar rats prevented early hepatic IR through inhibiting PKC/JNK activation; decreasing p-IRS (Ser307 ) and increasing p-IRS(Tyr612 ), p-Akt(Ser473 ) and p-GSK3(Ser9 ). These effects of RES were associated with reduced expression of acyl-CoA:glycerol-sn-3-phosphate acyltransferase (GPAT-1) and diacylglycerol:acyl-CoA acyltransferase (DGAT2), two critical enzymes in the glycerol-3-phosphate pathway for de novo triglycerides synthesis. These data indicate that RES protects against NAFLD, initially, by inhibiting the early development of hepatic IR. This article is protected by copyright. All rights reserved.