p62‐deficient mice developed obesity, insulin resistance, and fatty liver spontaneously in their later lives.[56, 57] p62 was shown to attenuate adipogenesis by inhibiting ERK signaling and macrophage inflammation in WAT while potentiating thermogenesis in BAT.[58] Meanwhile, p62 is essential for maintaining leptin sensitivity in the brain to control food intake.[59] Our study, for the first time, demonstrated that p62 is critical for modulating the Chchd10 reduction‐mediated adaptive response in white adipocytes by activating NRF2 activity. This evidence concerns the gene NFE2L2 and obesity due to melanocortin 4 receptor deficiency.