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. 2016 Aug 19;7:258.
doi: 10.3389/fphar.2016.00258. eCollection 2016.

Head to Head Comparison of Short-Term Treatment With the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice

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Free PMC article

Head to Head Comparison of Short-Term Treatment With the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice

Golam M Uddin et al. Front Pharmacol. .
Free PMC article

Abstract

Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD(+)). Recent studies have shown that NAD(+) levels can be increased by using the NAD(+) precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice. Sixty female 5 week old C57BL6/J mice were allocated across five groups: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group). After 6 weeks of diet, exercise groups underwent treadmill exercise (15 m/min for 45 min), 6 days per week for 6 weeks. NMN or vehicle (500 mg/kg body weight) was injected (i.p.) daily for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. The HFD significantly altered adiposity, glucose tolerance, plasma insulin, NADH levels and citrate synthase activity in muscle and liver. HEX and HNMN groups both showed significantly improved glucose tolerance compared to the HS group. NAD(+) levels were increased significantly both in muscle and liver by NMN whereas exercise increased NAD(+) only in muscle. Both NMN and exercise ameliorated the HFD-induced reduction in liver citrate synthase activity. However, exercise, but not NMN, ameliorated citrate synthase activity in muscle. Overall these data suggest that while exercise and NMN-supplementation can induce similar reversal of the glucose intolerance induced by obesity, they are associated with tissue-specific effects and differential alterations to mitochondrial function in muscle and liver.

Keywords: C57BL6 female mice; high fat diet; liver; mitochondria; muscle; nicotinamide mononucleotide; treadmill exercise.

Figures

FIGURE 1
FIGURE 1
Body weight of Chow sedentary (CS), Chow exercise (CEX), HFD sedentary (HS), HFD NMN (HNMN), and HFD exercise (HEX) mice over the experiment. Data are shown as mean ± SEM (n = 11–12/group). Data were analyzed by one way ANOVA followed by LSD post hoc test. **P < 0.01, ***P < 0.001 significant difference HS compared to CS.
FIGURE 2
FIGURE 2
Liver triglyceride (mg/g of tissue) of CS, CEX, HS, HNMN, and HEX mice. Data are shown as mean ± SEM (n = 9–11/group). Data were analyzed by one way ANOVA followed by LSD post hoc test. **P < 0.01 significant difference HS compared to CS. ∧∧∧P < 0.001 significant difference HNMN compared to HS. XXXP < 0.001 significant difference HEX compared to HS.
FIGURE 3
FIGURE 3
Glucose tolerance test (A, mmol/l) in CS (open circle) CEX (open triangle), HS (closed circle), HEX (closed triangle) and HNMN (closed square) mice, and (B) Area under the curve (mmol/l min). Data are shown as mean ± SEM (n = 11–12/group). Data were analyzed by one way ANOVA followed by LSD post hoc test. ***P < 0.001 significant difference HS compared to CS. ∧∧P < 0.01, ∧∧∧P < 0.001 significant difference HNMN compared to HS. XP < 0.05, XXP < 0.01, XXXP < 0.001 significant difference HEX compared to HS.
FIGURE 4
FIGURE 4
NAD+(A) and NADH (B) content (pmol/mg protein) of quadriceps muscle and liver (C,D) of CS, CEX, HS, HNMN, and HEX mice. Data are shown as mean ± SEM (n = 6–8/group). Data were analyzed by one way ANOVA followed by LSD post hoc test. *P < 0.05, **P < 0.01 significant difference HS compared to CS. ∧∧∧P < 0.001 significant difference HNMN compared to HS. XP < 0.05 significant difference HEX compared to HS.
FIGURE 5
FIGURE 5
Citrate synthase (μ mol/mg protein) and mtDNA copy (arbitrary number) in quadriceps muscle (A,C) and liver (B,D) of CS, CEX, HS, HNMN, and HEX mice. Data are shown as mean ± SEM (n = 9–11/group). Data were analyzed by one way ANOVA followed by LSD post hoc test. **P < 0.01, ***P < 0.001 significant difference HS compared to CS. ∧∧P < 0.01, ∧∧∧P < 0.001 significant difference HNMN compared to HS. XXXP < 0.001 significant difference HEX compared to HS.

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