The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity

Male Niacinamide 0301 basic medicine Physiology Biosynthesis Diet, High-Fat Mice 03 medical and health sciences Adipose Tissue, Brown Acid Animals Humans Obesity Energy-Expenditure Pathways Muscle, Skeletal Molecular Biology 2. Zero hunger Sirt1 Electron Transport Complex I Regulates Insulin-Secretion Beta-Cells Brain Acetylation Cell Biology NAD Mitochondria Pgc-1-Alpha Mice, Inbred C57BL HEK293 Cells Liver Organ Specificity Dietary Supplements Energy Metabolism Dependent Histone Deacetylase Receptor
DOI: 10.1016/j.cmet.2012.04.022 Publication Date: 2012-06-05T17:26:44Z
ABSTRACT
As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.
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