Nat. Rev. Endocrinol. doi: /nrendo

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Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.104 Figure 3 Schematic overview of the role of NAD+ in the regulation of mitochondrial metabolism Figure 3 | Schematic overview of the role of NAD+ in the regulation of mitochondrial metabolism. Exercise and caloric restriction directly and indirectly activate AMPK, thereby activating peroxisome proliferator-activated receptor γ co-activator 1 α (PGC-1α) while simultaneously promoting an increased NAD+ to NADH ratio and activating sirtuin 1 (SIRT1). Nutritional compounds such as resveratrol (RSV) can also activate SIRT1 through this route, whereas NAD+ precursors, such as nicotinamide riboside (NR), might directly elevate NAD+ levels through catalysis by nicotinamide phosphoribosyltransferase (NAMPT) and promote SIRT1 activity. The downstream outcome of activating these pathways converges onto an improved mitochondrial phenotype by multiple routes. Hesselink, M. K. C. et al. (2016) Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.104