1. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice.
- Author
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Yoshino J, Mills KF, Yoon MJ, and Imai S
- Subjects
- Animals, Circadian Rhythm genetics, Cytokines metabolism, Diabetes Mellitus, Type 2 metabolism, Disease Models, Animal, Gene Expression Regulation, Glucose metabolism, Hypoglycemic Agents pharmacology, Insulin metabolism, Lipid Metabolism, Mice, Nicotinamide Phosphoribosyltransferase metabolism, Oxidative Stress genetics, Sirtuin 1 metabolism, Aging, Diabetes Mellitus, Type 2 physiopathology, Diet, High-Fat, NAD biosynthesis, Nicotinamide Mononucleotide pharmacology
- Abstract
Type 2 diabetes (T2D) has become epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD(+) biosynthesis, and the NAD(+)-dependent protein deacetylase SIRT1. Here, we show that NAMPT-mediated NAD(+) biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD(+) intermediate, ameliorates glucose intolerance by restoring NAD(+) levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD(+) and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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