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). The gene discussed is IDO2; the disease is obesity due to melanocortin 4 receptor deficiency.