While OTUD3 regulates various genes involved in glucose and lipid metabolism by deubiquitinating and stabilizing peroxisome proliferator-activated receptor-delta (PPARδ), Otud3-deficient mice fed a high-fat diet developed greater obesity, dyslipidemia, and insulin resistance, suggesting that aberrant OTUD3 expression may be associated with obesity and a high risk of diabetes. Here, OTUD3 is linked to obesity due to melanocortin 4 receptor deficiency.