Attenuated PPARγ activity in heterozygous Pparg-deficient (Pparg+/−) C57Bl/6J mice protects against high-fat diet (HFD)-induced obesity, liver steatosis, and adipocyte hypertrophy; however, treatment with the PPARγ agonist pioglitazone (PGZ) abrogates the protection against adipocyte hypertrophy (enlarged adipocytes) and decreases insulin sensitivity (Kubota et al., 1999), suggesting a potential beneficial use for PPARγ antagonists to treat hepatic steatosis. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.