SESN2 was initially observed as a downstream effector of p53, and a myriad of adverse environmental stresses can induce SESN2 expression, such as oxidative stress, endoplasmic reticulum (ER) stress (ERS), energetic stress, and age- and obesity-associated metabolic pathologies (9, 53–58). This evidence concerns the gene SESN2 and obesity due to melanocortin 4 receptor deficiency.