Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.

Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI

Science 2021

1. Science. 2021 Jun 11;372(6547):1224-1229. doi: 10.1126/science.abe9985. Epub 2021 Apr 22. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Yoshino M(#)(1), Yoshino J(#)(1), Kayser BD(1), Patti GJ(2), Franczyk MP(1), Mills KF(3), Sindelar M(2), Pietka T(1), Patterson BW(1), Imai SI(3), Klein S(4). Author information: (1)Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA. (2)Department of Chemistry, Washington University School of Medicine, St. Louis, MO, USA. (3)Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA. (4)Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA. sklein@wustl.edu. (#)Contributed equally Comment in Science. 2021 Jun 11;372(6547):1147-1148. doi: 10.1126/science.abj0764. Cell Metab. 2021 Jul 6;33(7):1274-1275. doi: 10.1016/j.cmet.2021.06.008. Cardiovasc Res. 2021 Jul 27;117(9):e106-e109. doi: 10.1093/cvr/cvab212. Science. 2021 Jul 30;373(6554):eabj1696. doi: 10.1126/science.abj1696. In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239). Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. DOI: 10.1126/science.abe9985 PMCID: PMC8550608 PMID: 33888596 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: S.I. receives a part of patent-licensing fees from MetroBiotech (USA) and Teijin Limited (Japan) through Washington University. S.I. also serves as Invited Chief Scientist at the Institute for Biomedical Research and Innovation in Kobe, Japan, which does not involve competing interests. J.Y. is an inventor of a patent application related to NMN (#20180228824). S.K. receives research support from Janssen Pharmaceuticals and serves on a scientific advisory board for Merck Sharp & Dohme Corp. The other authors have nothing to disclose.