In the present study, we discovered 2 effects of skeletal muscle–specific activation of the PERK pathway by using the Fv2E-PERK system: PERK activation affects the level of amino acids necessary for antioxidant synthesis, and PERK activation confers some resistance to diet-induced obesity through the secretion of fibroblast growth factor (FGF)21 as a myokine that promotes energy consumption in brown adipose tissue (BAT). Here, EIF2AK3 is linked to Obesity.