|
Status |
Public on Dec 05, 2011 |
Title |
Nicotinamide mononucleotide, a key NAD+ precursor, treats the pathophysiology of diet- and age-induced diabetes |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
|
Summary |
Type 2 diabetes (T2D) has become an 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 novel intervention against diet- and age-induced T2D.
|
|
|
Overall design |
4 regular chow fed mice (RC1-4) vs 4 high-fat diet fed (HFD) (HFD1a-4a) mice were analyzed on one chip (Chip-A). 4 HFD mice (HFD1b-4b) vs 4 HFD-NMN treated mice (NMN1-4) were examined on the other chip (Chip-B).
|
|
|
Contributor(s) |
Yoshino J, Imai S, Mills KF, Yoon MJ |
Citation(s) |
- Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab 2011 Oct 5;14(4):528-36. PMID: 21982712
|
|
Submission date |
Aug 25, 2011 |
Last update date |
Sep 15, 2023 |
Contact name |
Jun Yoshino |
E-mail(s) |
jyoshino@med.shimane-u.ac.jp
|
Organization name |
Faculty of Medicine, Shimane University
|
Street address |
89-1 Enya-cho
|
City |
Izumo |
State/province |
Shimane |
ZIP/Postal code |
693-8501 |
Country |
Japan |
|
|
Platforms (1) |
GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
|
Samples (16)
|
|
Relations |
BioProject |
PRJNA145417 |