In this study, using FGF21-deficient mice fed an HFD, we showed that levels of atrophic markers such as MuRF1 and Atrogin-1 were markedly increased at the transcript and protein levels in FGF21-deficient obese mice, implicating that deficiency of FGF21 aggravates obesity-induced skeletal muscle atrophy. This evidence concerns the gene TRIM63 and obesity due to melanocortin 4 receptor deficiency.