Accumulating reports provide evidence for a novel homeostatic function of GRP78 in mediating fatty acid oxidation and steroidogenesis.[61, 62] Specific overexpression of GRP78 in hypothalamus could revert HFD‐induced obesity by promoting BAT thermogenesis and beige formation in iWAT.[63, 64] However, our study demonstrated that cell membrane translocation of GRP78 played a role in releasing the metabolic stress of over‐nutrition. This evidence concerns the gene HSPA5 and Obesity.