Dominant-negative mutations in human PPARγ can lead to severe metabolic syndrome, insulin resistance, and diabetes at an unusually young age [419,420], and several point mutations in the PPARγ gene are associated with severe insulin resistance (with or without T2D) and familial partial lipodystrophy phenotypes [421,422,423,424,425]. This evidence concerns the gene PPARG and familial partial lipodystrophy.