Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice

Jun Yoshino, Kathryn F. Mills, Myeong Jin Yoon, Shin Ichiro Imai

Research output: Contribution to journalArticle

534 Scopus citations

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.

Original languageEnglish
Pages (from-to)528-536
Number of pages9
JournalCell metabolism
Volume14
Issue number4
DOIs
StatePublished - Oct 5 2011

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