Taken together, these data support the hypothesis that pnpla3 in rat liver primarily acts in a lipogenic role through fatty acid esterification at the level of LPA acyltransferase and that decreasing pnpla3 expression prevents lipid-induced whole body insulin resistance by preventing lipid-induced hepatic insulin resistance by decreasing hepatic DAG accumulation and activation of PKCε. The gene discussed is PNPLA3; the disease is Insulin resistance.