Abstract
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 the 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. Female offspring weaned onto HFD were given treadmill exercise for 9 weeks, or NMN injection daily for 18 days. 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). This work encourages further study to confirm the suitability of NMN for use in reversing metabolic dysfunction linked to programming by maternal obesity.
Highlights
Over the last three decades, globally, the proportion of adults with a body mass index of >25 has increased to approximately 37% and 38% in men and women respectively[1]
We wanted to test whether physical exercise or nicotinamide mononucleotide (NMN) treatment in offspring of obese mothers would improve metabolism, as we have previously shown in female mice exposed to diet induced obesity[26]
These differences were in final body weight, organ weights, Glucose tolerance test (GTT), plasma insulin, liver triglyceride and Pparg transcript levels
Summary
Over the last three decades, globally, the proportion of adults with a body mass index of >25 has increased to approximately 37% and 38% in men and women respectively[1]. There are multiple explanations for these associations such as the shared environment (e.g. diet) and genetics of parent and child[6], a key contributor is the alteration of developmental and metabolic processes in offspring in early life through ‘developmental’ or ‘gestational programming’[6,7,8]. These alterations in glucose and fat metabolism, and appetite regulation can predispose offspring to obesity in adolescence or adulthood[6,7,8]. It is thought that many of the benefits of exercise and of fasting stem from increasing NAD+, which stimulates mitochondrial function leading to burning of fat and carbohydrate stores[33,34]
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