According to latest studies, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene accounts for the largest fraction of genetic predisposition to NAFLD; in particular, the carriage of the I148M variant is associated with hepatic fat accumulation, a reduction in adiponectin, and a direct impact on adiposity and insulin resistance. Here, PNPLA3 is linked to Insulin resistance.