Expression of Ppargc1a is reduced in insulin resistant tissues [40], during obesity [47] and in type 2 diabetes [48]; and Ppargc1a knock-out mice exhibit hepatic steatosis due to a reduction in mitochondrial oxidative capacity and mtDNA content, together with an upregulation of lipogenic gene expression [49]. The gene discussed is PPARGC1A; the disease is obesity due to melanocortin 4 receptor deficiency.