Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise
Golam Mezbah Uddin, Neil A. Youngson, Bronte M. Doyle, David A. Sinclair & Margaret J. Morris
Maternal overnutrition increases the risk of long-term metabolic dysfunction in offspring. Exercise improves metabolism partly by upregulating mitochondrial biogenesis or function, via increased levels of nicotinamide adenine dinucleotide (NAD+). We have shown that the NAD+ precursor, nicotinamide mononucleotide (NMN) can reverse some of thOur results also suggest that improved fat metabolism in liver due to post-weaning NMN supplementation and exercise are significant contributors to the overall improvements in adiposity. Te negative consequences of high fat diet (HFD) consumption. To investigate whether NMN can impact developmentally-set metabolic deficits, we compared treadmill exercise and NMN injection in offspring of obese mothers.
Five week old lean and obese female C57BL6/J mice were mated with chow fed males. .. After 6 weeks of post-weaning diet, offspring from HFD fed mothers were further distributed into either sedentary, exercise, or NMN groups thus generating 6 groups:
HFD-Chow-sedentary HCS;
HFD-Chow-exercise HCX;
HFD-Chow-NMN HCN;
HFD-HFD-sedentary HHS;
HFD-HFD-exercise HHX;
HFD-HFD-NMN HHN
Offspring from chow mothers remained in their chow or HFD groups: Chow-Chow-sedentary: CCS; Chow-HFD-sedentary: CHS.
Maternal obesity programmed increased adiposity and liver triglycerides, with decreased glucose tolerance, liver NAD+ levels and citrate synthase activity in offspring. Both interventions reduced adiposity, and showed a modest improvement in glucose tolerance and improved markers of mitochondrial function. NMN appeared to have stronger effects on liver fat catabolism (Hadh) and synthesis (Fasn) than exercise. The interventions appeared to exert the most global benefit in mice that were most metabolically challenged (HFD-consuming offspring of obese mothers).
No significant effect of intervention [on glucose tolerance] was observed in offspring consuming chow (Fig. 1F). In siblings consuming HFD, exercise and NMN improved the late phase of the response to glucose challenge (Fig. 1G). Measurement of the area under the curve (not shown) suggested that there are beneficial effects of both interventions. However only exercise reached significance (HHS vs HHEX P = 0.009; HHS vs HHN P = 0.059). ...
Both maternal and post-weaning diet had significant impacts on plasma insulin. Maternal and post weaning HFD increased [fasting] plasma insulin concentration (Table 1). Furthermore, NMN significantly increased insulin concentration regardless of their diet (Table 2). ... [On its face, this would be a bad thing —MR] ...
The improvement of glucose tolerance in exercise is most likely due to improved insulin sensitivity and glucose uptake, especially by skeletal muscle53. In contrast, our data suggest that NMN supplementation may increase clearance of glucose from the circulation by increasing plasma insulin levels. It is unclear whether the heightened plasma insulin in our cohort is explained by Sirt1-mediated increases in pancreatic islet beta cell mass54 or by increased Sirt1-mediated insulin secretion, as NMN was administered 4 hours prior to sacrifice. ...
Our results also suggest that improved fat metabolism in liver due to post-weaning NMN supplementation and exercise are significant contributors to the overall improvements in adiposity. ...
Edited by Michael, 10 November 2017 - 06:31 PM.