Obese conditions in mice has been observed to activate CRTC2/3 by decreasing the expression of salt-inducible kinases (SIK), a Ser/Thr kinase that phosphorylates and inhibits CRTCs.343 Tumor necrosis factor α (TNF-α) mediated PGC-1α downregulation has been reported in obesity in rodents. This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.