Further supporting the involvement of inflammatory cues in mitochondrial biogenesis dysregulation, a study revealed that lower mRNA expression of Ppargc1a, Nrf1, and Tfam, accompanied by lower expression of eNOS, was ameliorated by TNFα signaling deficiency in the SM of different rodent models of obesity [66]. Here, NOS3 is linked to obesity due to melanocortin 4 receptor deficiency.