Unlike the conventional Ido−/− mice, the Ido1-lKO mice following a 12-week of HFD induction exhibited comparative bodyweight change (Supplementary Fig. 5b, c) and insulin sensitivity (Supplementary Fig. 5d, e) as their littermates, confirming that macrophages are not the critical target for IDO1 modulation of the development of obesity. Here, IDO1 is linked to obesity due to melanocortin 4 receptor deficiency.