The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity

Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, Brown / pathology
  • Animals
  • Brain / metabolism
  • Diet, High-Fat / adverse effects*
  • Dietary Supplements
  • Electron Transport Complex I / metabolism
  • Energy Metabolism
  • HEK293 Cells
  • Humans
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • NAD / blood
  • NAD / metabolism*
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Obesity / etiology
  • Obesity / prevention & control*
  • Organ Specificity
  • Oxidation-Reduction
  • Oxygen Consumption
  • Protein Processing, Post-Translational
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Nicotinic / metabolism
  • Sirtuin 1 / metabolism
  • Sirtuin 3 / metabolism
  • Superoxide Dismutase / metabolism
  • Weight Gain / drug effects

Substances

  • HCAR2 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • nicotinamide-beta-riboside
  • NAD
  • Niacinamide
  • Superoxide Dismutase
  • superoxide dismutase 2
  • SIRT1 protein, human
  • SIRT3 protein, human
  • Sirtuin 1
  • Sirtuin 3
  • Electron Transport Complex I
  • NDUFA9 protein, human