To explore the potential roles of ANGPTL8 in the progression of diet-induced obesity, we first constructed ANGPTL8 knockout mice (KO) (Supplementary Figures 1A–C) and investigated the impact of ANGPTL8 on body fat synthesis to induce lipid deposition in multiple organs of ANGPTL8 KO and WT mice after 10 and 20 months (10 M and 20 M) of NCD or HFD. This evidence concerns the gene ANGPTL8 and obesity due to melanocortin 4 receptor deficiency.