Pereira et al. (170) demonstrated that a muscle deficiency of the mitochondrial fusion protein optic atrophy 1 (OPA1) alters mitochondrial dynamics and increases endoplasmic reticulum (ER) stress, thereby promoting muscle-FGF21 release and rendering mice resistant to age- and diet-induced obesity and insulin resistance. The gene discussed is OPA1; the disease is obesity due to melanocortin 4 receptor deficiency.