PPARGC1A and obesity due to melanocortin 4 receptor deficiency: Osteoarthritis, the most prevalent chronic joint disease, is a major source of pain, disability, and socioeconomic cost worldwide in accordance with the increased aging population and the epidemic of obesity.538 Notably, the upregulation of PGC-1α by activating the upstream molecule or coactivating the partners, remarkably reverses impaired mitochondrial biogenesis, oxidative stress, and inflammation in osteoarthritis.539–544 Nevertheless, classical drug therapy may be too late to help due to the relatively late diagnosis during the osteoarthritis process.