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 pretreatment in 3 days HFD-fed adult Wistar rats prevented early hepatic IR through inhibiting PKC/JNK activation; decreasing p-IRS (Ser(307)) and increasing p-IRS(Tyr(612)), p-Akt(Ser(473)) and p-GSK3(Ser(9)). 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.