Abstract
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, and subsequent increases in nicotinamide adenine dinucleotide (NAD+), an important metabolic cofactor. 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. However, the effects of combined exercise and NMN supplementation are unknown. Thus here we examined the combined effects of NMN and treadmill exercise in female mice with established obesity after 10 weeks of diet. Five-week old female C57BL/6J mice were exposed to control diet (n=16) or HFD. Sedentary mice fed HFD were either untreated (HFD; n=16), received NMN in drinking water (400mg/kg; HNMN; n=16), were exposed to treadmill exercise 6 days/week (HEx; n=16) or exercise combined with NMN (HNEx; n=16). Whilst some metabolic benefits of NMN have been described, at this dose, NMN administration impaired several aspects of exercise-induced benefits in obese mice, including glucose tolerance, glucose stimulated insulin secretion from islets and reduced hepatic triglyceride accumulation. HNEx mice also exhibited 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. Our data show that NMN treatment impedes the beneficial metabolic effects of exercise in a mouse model of diet-induced obesity in association with disturbances in redox metabolism.
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