SMAD1 and obesity due to melanocortin 4 receptor deficiency: Notably, previous knockout experiments in mouse have shown decreased abdominal adipose tissue amount, decreased subcutaneous adipose tissue amount, abnormal adipose tissue development, and lipodystrophy with a knockout of Sh3pxd2b,72,73 and decreased total body fat amount and decreased susceptibility to diet-induced obesity with a knockout of Ahnak. 87The Ahnak gene directly interacts with Smad1 on the Pparγ2 promoter, increasing the expression of Pparγ2, an adipose tissue-specific isoform of Pparγ. 88Pparγ is a major regulator of adipogenesis promoting genes.89