SIRT1 and obesity due to melanocortin 4 receptor deficiency: In obesity, SIRT1 activity is reduced in Bone marrow-derived dendritic cells (DCs), with elevated extracellular acidification rates (ECAR)/oxidative phosphorylation (OXPHOS), increased Major histocompatibility complex class II (MHCII)/CD86/CD40, higher IL-12p40 and lower TGF-β, coincident with suppression of the IDO1–kynurenine pathway; mechanistically, SIRT1 positively regulates Ido1 in a PPARγ-dependent manner, positioning SIRT1 as a gatekeeper of tryptophan catabolism and T-cell polarization (180).