Nicotinamide Mononucleotide Intake Reduces Impact of Maternal Obesity in Offspring

Written by Angeline A. De Leon, Staff Writer. Using a mouse model, researchers demonstrate an association between maternal obesity and metabolic dysfunction markers that can be reversed in offspring with exercise and NMN supplementation.

Over just the last three decades, the number of obese adults worldwide has risen to nearly 40%, for both men and women ¹. The prevalence of obesity among children has dramatically increased as well, leading to increased risk of metabolic disorders, such as type 2 diabetes, hypertension, and non-alcoholic fatty liver disease, later on in life ². Epidemiological research suggests an association between maternal obesity and increased risk of obesity in offspring later on ³. Correspondingly, pharmacological research indicates that treatment of maternal obesity during pregnancy can decrease the likelihood of metabolic dysfunction in infants ⁴. At a biochemical level, obesity involves reduced levels of nicotinamide adenine dinucleotide (NAD⁺), a critical coenzyme in metabolic processes ⁵. Research also suggests that the metabolic benefits of physical activity and fasting are critically tied to their ability to boost NAD⁺, which can stimulate the burning of fat stores ^6,7. Nicotinamide mononucleotide (NMN) is a precursor of NAD⁺ which has been successfully used in the therapeutic treatment of metabolic disorders ⁸. Experimental studies show that NMN supplementation can effectively increase NAD⁺ levels and improve glucose metabolism in obese mice ^6,9. However, it is unknown whether NMN is capable of reversing obesity-related metabolic deficits programmed in offspring prior to birth. Thus, in a 2017 study ¹⁰ published in Scientific Reports, researchers examined the effects of NMN administration in a rodent model of obesity, comparing the impact of NMN vs. exercise on markers of metabolic dysfunction in the offspring of obese mothers.

A litter of 128 3-week-old female mice were assigned to receive either control chow or high-fat diet (HFD) pellets daily for 5 weeks. Females were mated with males over a 7-day period, and subsequent offspring of HFD-fed mothers were given a post-weaning diet of either regular chow or HFD before being assigned to sedentary behavior, treadmill exercise for 9 weeks, or daily NMN injection for 18 days.  Mothers were sacrificed in order to harvest tissue samples for analyses, and at 17 weeks of age, offspring underwent a glucose tolerance test (GTT). Blood samples were also collected and offspring sacrificed at 19 weeks of age in order to determine plasma insulin concentration, liver triglyceride levels, liver NAD⁺ levels, and citrate synthase activity (marker of mitochondrial function). Adiposity was also measured based on white adipose tissue mass.

As expected, maternal HFD was significantly associated with increased body weight, liver weight, and adipose tissue mass in offspring, as well as elevated plasma insulin concentrations and liver triglyceride levels (p < 0.001 for all). In the most metabolically-challenged mice (offspring of HFD-fed mothers assigned to HFD themselves), both exercise and NMN supplementation appeared to significantly improve offspring body weight, white tissue adiposity, and liver triglycerides (p range = 0.001-0.05 for both interventions). NMN supplementation also showed stronger positive effects on citrate synthase activity (p < 0.05) and liver NAD⁺ levels (p < 0.001) over exercise.

Research findings are in line with previous studies reporting a link between maternal obesity and metabolic dysfunction in offspring  ^4,  5 .   Data also suggest that early intervention with exercise and NMN supplementation can effectively reverse many of the programmed metabolic deficits in young. Both programs proved capable of reducing body weight, adiposity, hepatic fat, as well as markers of mitochondrial function in offspring that were the most metabolically challenged, stronger effects being notably associated with NMN. Next steps in research would involve investigating the longer-term impact of NMN treatment for obesity and carrying out translational research in overweight human subjects.

Source: Uddin GM, Youngson NA, Doyle BM, et al. Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise. Scientific Reports. 2017; 7: 15063. DOI: 10.1038/s41598-017-14866-z.

© The Author(s) 2017. This Open Access article is licensed under a Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0/.

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Posted December 1, 2020.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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