Although circulating ANGPTL8 levels have been reported to be related to IR [26], T2DM [27–30], obesity [27, 30], PCOS [31–33], nonalcoholic fatty liver disease (NAFLD) [34], and MetS [12, 35], ANGPTL8 is mainly secreted and expressed by hepatocytes. Here, ANGPTL8 is linked to obesity due to melanocortin 4 receptor deficiency.