Consistent with impairments in adipose insulin sensitivity as a putative mechanism for HCC in Adipo-KO mice, the fat-specific insulin receptor knockout (FIRKO) or FIRKO in combination with insulin-like growth factor-1 receptor–KO mice also exhibit lipodystrophic phenotypes, and similarly, develop liver tumors with aging (81, 82). Here, INS is linked to hepatocellular carcinoma.