TY - JOUR T1 - EXERCISE-INDUCED BENEFITS ON GLUCOSE HANDLING IN A MODEL OF DIET-INDUCED OBESITY ARE REDUCED BY CONCURRENT NICOTINAMIDE MONONUCLEOTIDE JF - bioRxiv DO - 10.1101/2020.06.22.164459 SP - 2020.06.22.164459 AU - Josephine Yu AU - D. Ross Laybutt AU - Lynn-Jee Kim AU - Lake-Ee Quek AU - Lindsay E. Wu AU - Margaret J. Morris AU - Neil A. Youngson Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/23/2020.06.22.164459.abstract N2 - Objective Almost 40% of adults worldwide are classified as overweight or obese. Exercise is a beneficial intervention in obesity, partly due to increases in mitochondrial activity, with a potential role for the concomitant increase in nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that increasing NAD+ levels through pharmacological supplementation with precursors such as nicotinamide mononucleotide (NMN) improved metabolic health in high fat diet (HFD) fed mice. We examined the combined effects of NMN and treadmill exercise on the metabolic dysregulation in HFD-induced obesity.Methods Five-week old female C57BL/6J mice were exposed to control diet or HFD. Mice fed HFD were treated with NMN in drinking water (400mg/kg; HNMN), treadmill exercise (HEx) or combined NMN and exercise (HNEx).Results Unexpectedly, NMN administration impaired several aspects of exercise-induced benefits in HFD mice, including glucose tolerance, glucose stimulated insulin secretion from islets and reduced hepatic triglyceride accumulation. Mechanistically, HNEx mice displayed increased antioxidant and reduced prooxidant gene expression in both islets and muscle, suggesting that altered redox status is associated with the loss of exercise-induced health benefits with NMN co-treatment.Conclusion Our data show that NMN treatment blocks the beneficial metabolic effects of exercise in a mouse model of diet-induced obesity in association with disturbances in redox metabolism.HighlightsNMN dampened exercise-induced benefits on glucose handling in diet-induced obesity.NMN administration in exercise enhanced ratio of antioxidants to prooxidants.We suggest NMN administration may not be beneficial when NAD+ levels are replete.Competing Interest StatementL.E.W. is an inventor on patents licensed to Metro Biotech NSW and to Jumpstart Fertility, and has received sponsored research funding from both companies. He is an advisor and shareholder in EdenRoc Sciences (Metro Biotech NSW, Metro Biotech, Liberty Biosecurity), Life Biosciences LLC and its daughter companies (Jumpstart Fertility, Continuum Biosciences, Senolytic Therapeutics, Selphagy, Animal Biosciences, Iduna) and in Intravital Pty Ltd. L.E.W. provides consulting work for Life Biosciences. ER -