However, results from adult clinical studies were controversial, for example, some studies reported that circulating betatrophin levels were positively correlated with HbA1c [11, 14] and increased in T2DM [11–14], while others exhibited decreased betatrophin concentrations in T2DM as well as obesity [15, 22]. Here, ANGPTL8 is linked to obesity due to melanocortin 4 receptor deficiency.