We have previously shown that mice lacking the CDK6 kinase domain (K43M) exhibited metabolic reprogramming (Hou et al., 2018) as manifested by increased white fat browning, reduced fat mass in both SAT and VAT, more resistance to high fat diet (HFD)-induced obesity, improved metabolic profiles, and enhanced insulin sensitivity (Hou et al., 2018). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.