The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.
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.
École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Carles
C
Cantó
Riekelt H
RH
Houtkooper
Eija
E
Pirinen
Dou Y
DY
Youn
Maaike H
MH
Oosterveer
Yana
Y
Cen
Pablo J
PJ
Fernandez-Marcos
Hiroyasu
H
Yamamoto
Pénélope A
PA
Andreux
Philippe
P
Cettour-Rose
Karl
K
Gademann
Chris
C
Rinsch
Kristina
K
Schoonjans
Anthony A
AA
Sauve
Johan
J
Auwerx
D000107:Acetylation; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D042967:Electron Transport Complex I / Q000378:metabolism; D004734:Energy Metabolism; D057809:HEK293 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000097:blood / Q000378:metabolism*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*; D009928:Organ Specificity; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011499:Protein Processing, Post-Translational; D011726:Pyridinium Compounds; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D000099156:Superoxide Dismutase 2
D042967:Electron Transport Complex I; D009243:NAD; D009536:Niacinamide; D011726:Pyridinium Compounds; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D056564:Sirtuin 1; D056566:Sirtuin 3; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C530636:HCAR2 protein, human; C018613:nicotinamide-beta-riboside; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; C571164:NDUFA9 protein, human