Knockdown of the E3 ubiquitin ligase IDOL in mice decreased circulating levels of cholesterol, triglycerides, hepatosteatosis and fat mass.293 Deletion of TRIM28 induces obesity via epigenetic mechanisms in embryonic development.294 TRIM72/MG53 deficiency targets the insulin receptor and IRS1 protein to attenuate HFD-induced obesity.295. Here, IRS1 is linked to obesity due to melanocortin 4 receptor deficiency.