PNPLA3 and metabolic dysfunction-associated steatotic liver disease: Previous studies have implicated DAG-mediated activation of PKCε as causing hepatic insulin resistance in NAFLD.1, 26, 28 Consistent with this mechanism in the pnpla3 ASO-treated rats, we observed an ∼50% reduction in hepatic membrane DAG content and PKCε activation (Fig. 4B,C).