In contrast, autophagy knockout in skeletal muscle cells led to the induction of fibroblast growth factor 21 (FGF21) as a “mitokine” due to mitochondrial stress and resistance to diet-induced obesity and insulin resistance7, in contrast to the expectation that autophagy deficiency associated with mitochondrial dysfunction in insulin target tissues would lead to insulin resistance. The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.