This study provides strong genetic evidence in support of the hypothesis that increased plasma APOC3 concentrations predispose lean individuals to NAFLD associated with hepatic insulin resistance.9 Importantly, the development of NAFLD associated with hepatic insulin resistance in response to dietary alterations exemplifies how gene-environment interactions contribute to the pathogenesis of complex phenotypes. This evidence concerns the gene APOC3 and metabolic dysfunction-associated steatotic liver disease.