Recently, Zhu, H. et al. have demonstrated in a mouse model of diet-induced obesity, that the CRISPRa-based activation of Fgf21 and Fndc5 in skeletal muscle can improve obesity by increasing the secretion of FGF21 and irisin by myocytes and the browning of white adipocytes through the induction of UCP-1 expression [191]. Here, FNDC5 is linked to obesity due to melanocortin 4 receptor deficiency.