Although both humans and mice with obesity-associated hepatic steatosis display PTEN downregulation in the liver [39,40] and usually IR [41], the total abrogation of PTEN in mouse livers, on the contrary, triggers muscle insulin hypersensitivity and decreased adiposity despite the presence of a large steatosis [34]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.