Xu et al. found that excess cholesterol can reduce insulin exocytosis through a dynamic-dependent process activated by phosphatidylinositol 4,5-bisphosphate.430 Meanwhile, cholesterol accumulation also induces apoptosis of pancreatic β cells by enhancing mitochondrial bioenergetic damage, inflammation, oxidative stress and ER stress.431–433 In addition, imbalanced cholesterol homeostasis in β cells increases obesity, reduces skeletal muscle mass and causes systemic inflammation.434 This may provide a new explanation for the link between diabetes and obesity. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.