The World Health Organization predicts that by 2015, 75% of the adult population will be overweight. Exercise has known beneficial effects on the metabolic outcomes of obesity. Exercise improves metabolism by up-regulating mitochondrial activity, through increased levels of nicotinamide adenine dinucleotide (NAD+). Recent studies suggest that the NAD+ precursor nicotinamide mononucleotide (NMN) acts as an exercise mimetic by increasing NAD+ levels. Several studies have demonstrated that exercise improves mitochondrial function and biogenesis in muscle. Here we compared the effects of exercise and NMN on the metabolic consequences of high-fat diet (HFD) induced obesity.
60 Female C57BL6/J mice were allocated across 5 interventions: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD Exercise: HEX (12/group). After 6 weeks of diet, HFD mice weighed 22% more than chow fed mice. Then the exercise groups underwent treadmill exercise (15m/min for 45 minutes), 6 days per week for 6 weeks. NMN (500mg/kg body weight) was injected (IP) every day for the last 17 days before they were sacrificed. A glucose tolerance test (GTT) (2g/kg body weight) was carried out. Mitochondrial DNA copy number was measured by quantitative PCR and citrate synthase activity was measured in quadriceps muscle.
The GTT showed that HEX and HNMN both had significantly improved plasma glucose clearance compared to the HS group. Phenotypic data showed no significant alteration to body weight due to exercise or NMN in the HFD groups. Mitochondrial copy number was significantly increased by NMN treatment but not by exercise. However, exercise, but not NMN, significantly ameliorated the HFD-induced reduction in muscle citrate synthase activity.
Overall the study showed that exercise and NMN improve glucose tolerance through different mechanisms involving mitochondria in a HFD induced obese mouse model.