Sgk3-KO mice exhibited protection from obesity induced by glucocorticoid or a high-fat diet (HFD), and SGK3 PROTAC also showed anti-adipogenesis effects on HFD-induced obesity, suggesting that inhibiting SGK3 could potentially ameliorate glucocorticoid-induced metabolic defects. Here, SGK3 is linked to obesity due to melanocortin 4 receptor deficiency.