INS and obesity due to melanocortin 4 receptor deficiency: In obese humans or rats fed high fat, the levels of mitophagy-related signals LC3BII, Parkin, FUNDC1, and BNIP3 are decreased, suggesting that mitophagy may be causally related to obesity and insulin resistance.330,331 Ablation of FUNDC1 brings about defective mitophagy in anabolic white adipose tissue (WAT), leading to massive ROS generation, which resulting in oxidative stress-driven MAPK activation.332 Furthermore, MAPK activation blocks insulin signaling, resulting in insulin resistance in other insulin-responsive organs.