期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 69, 期 5, 页码 1555-1566出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.0c07831
关键词
NAD(+); NAMPT; peptides; metabolism; IRW
资金
- Natural Sciences and Engineering Research Council (NSERC) of Canada
- Egg Farmers of Canada
- CIHR [PS-391979]
IRW, derived from ovotransferrin, acts as a small peptide booster of NAMPT levels, increasing intracellular NAMPT protein levels and NAD(+) to counter the effects of aging and metabolic disease.
Nicotinamide adenine dinucleotide (NAD(+)) plays a vital role in cellular processes that govern human health and disease. Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in NAD(+) biosynthesis. Thus, boosting NAD(+) level via an increase in NAMPT levels is an attractive approach for countering the effects of aging and metabolic disease. This study aimed to establish IRW (Ile-Arg-Trp), a small tripeptide derived from ovotransferrin, as a booster of NAMPT levels. Treatment of muscle (L6) cells with IRW increased intracellular NAMPT protein levels (2.2-fold, p < 0.05) and boosted NAD(+) (p < 0.01). Both immunoprecipitation and recombinant NAMPT assays indicated the possible NAMPT-activating ability of IRW (p < 0.01). Similarly, IRW increased NAMPT mRNA and protein levels in the liver (2.6-fold, p < 0.01) and muscle tissues (2.3-fold, p < 0.05) of C57BL/6J mice fed with a high-fat diet (HFD). A significantly increased level of circulating NAD(+) was also observed following IRW treatment (4.7 fold, p < 0.0001). Dosing of Drosophila melanogaster with IRW elevated both D-NAAM (fly NAMPT) and NAD(+) in vivo (p < 0.05). However, IRW treatment did not boost NAMPT levels in SIRT1 KO cells, indicating a possible SIRT1 dependency for the pharmacological effect. Overall, these data indicate that IRW is a novel small peptide booster of the NAMPT pool.
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