Publication

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

Résumé

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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Concepts associés (32)
Métabolisme des glucides
Le métabolisme des glucides est l'ensemble des processus biochimiques responsables de la formation, la dégradation et de l'interconversion des glucides chez les organismes vivants. Le glucide le plus important est le glucose, un sucre simple (ose) qui est métabolisé par presque tous les organismes connus. Le glucose et d'autres glucides participent à une grande variété de voies métaboliques présentes chez toutes les espèces vivantes : les plantes synthétisent grâce à la photosynthèse des glucides (amidon) à partir du présent dans l'atmosphère terrestre.
Lipid metabolism
Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown and storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In animals, these fats are obtained from food and are synthesized by the liver. Lipogenesis is the process of synthesizing these fats. The majority of lipids found in the human body from ingesting food are triglycerides and cholesterol.
Respiration cellulaire
redresse=2|vignette|Schéma de principe de la phosphorylation oxydative dans une mitochondrie illustrant l'intégration du cycle de Krebs avec la chaîne respiratoire, et le couplage de celle-ci avec l'ATP synthase au moyen d'un gradient électrochimique issu d'un gradient de concentration de protons à travers la membrane mitochondriale interne. La respiration cellulaire est l'ensemble des processus du métabolisme cellulaire convertissant l'énergie chimique contenue dans le glucose en adénosine triphosphate (ATP).
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