These findings are consistent with previous observations demonstrating improved glucose tolerance in HFF pnpla3 knockout mice and in obese mice with decreased hepatic pnpla3 expression by siRNA injection, although no physiological or cellular mechanism was provided.15, 17 In this regard, we found that pnpla3 ASO-treated rats were primarily protected from lipid-induced hepatic insulin resistance without improvements in insulin-stimulated peripheral glucose metabolism. This evidence concerns the gene PNPLA3 and Insulin resistance.