The production of irisin phosphorylates p38 MAPK and activates extracellular signal-regulated kinase (ERK), thereby leading to white fat browning, increased energy expenditure, and upregulation of uncoupling protein 1 (UCP1), thus alleviating HFD-induced obesity and insulin resistance in vivo [49]. The gene discussed is FNDC5; the disease is obesity due to melanocortin 4 receptor deficiency.