Resveratrol protects against hepatic insulin resistance in a rat's model of non‐alcoholic fatty liver disease by down‐regulation of GPAT GPAT ‐1 and DGAT DGAT 2 expression and inhibition of PKC PKC membranous translocation

摘要

Summary 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‐ GSK 3(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 ( DGAT 2), 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 .