PNPLA3 and fatty liver disease: Mutations in APOB lead to hepatic steatosis but are not associated with increased HOMA-IR33 or reduced insulin-mediated glucose disposal.34 Similarly, the I148M allele of PNPLA3 has been systematically associated with increased liver TG content but not with insulin resistance as determined by HOMA-IR or euglycemic clamp studies.4 Thus, increased liver TG content per se does not lead to insulin resistance.