IDO1 and obesity due to melanocortin 4 receptor deficiency: Corroborating the observation of less inflammatory response in HFD compared with obese WT mice, Endo1-KO mice on HFD showed a significant drop in the activity of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO), which is a key enzyme involved in the degradation of tryptophan (TRP) metabolism to kynurenine (KYN), and the activity of which is strongly induced by proinflammatory cytokines in obesity (23) (Figure 4B).