The SIRT2- PGC-1α regulatory axis is negatively regulated by HIF-1α, which negates the intrinsic pathways of fatty acid catabolism in adipocytes and creates a metabolic state that supports the development of obesity.867 SIRT6 overexpression was found to exacerbate diet-induced obesity by decreasing STAT3 acetylation and lowering pro-opiomelanocortin expression in the hypothalamus.868. This evidence concerns the gene PPARGC1A and obesity due to melanocortin 4 receptor deficiency.