PPARGC1A and obesity due to melanocortin 4 receptor deficiency: Furthermore, Pgc-1α expression is reduced in patients with T2D and obesity, and this reduction seems to be one of the factors responsible for the development and progression of T2D [93,121,122,123], as downstream PGC-1α target genes involved in oxidative phosphorylation are also downregulated in the skeletal muscle of T2D patients [122].