Therefore, we aimed to investigate whether: (a) hepatic PNPLA3 expression correlates with fibrosis progression in human NASH and according to the I148M genotype; (b) PNPLA3 expression is regulated by glucose and FFAs in hepatocytes as well as in HSCs; (c) metabolic stress in hepatocytes affects PNPLA3 expression and fibrogenic features in HSCs. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatohepatitis.