PNPLA3 and obesity due to melanocortin 4 receptor deficiency: In fact, the expression of PNPLA3 is directly regulated by the insulin-regulated transcription factor sterol regulatory element-binding protein-1c (SREBP-1c), and pathogenic PNPLA3 mutant products accumulate under conditions of obesity and insulin resistance, thus exacerbating liver steatosis, inflammation, and cirrhosis (Huang et al., 2010).