Understanding the Impact of Maternal Obesity on Offspring Metabolism and Potential Interventions
Introduction:
- Maternal overnutrition increases the risk of long-term metabolic dysfunction in offspring.
- Exercise improves metabolism by upregulating mitochondrial biogenesis or function.
- Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), can reverse negative consequences of high fat diet (HFD) consumption.
Examining the Effects of Exercise and NMN in Offspring of Obese Mothers:
- The study compared the effects of treadmill exercise and NMN injection in offspring of obese mothers.
- Maternal obesity resulted in increased adiposity, liver triglycerides, decreased glucose tolerance, liver NAD+ levels, and citrate synthase activity in offspring.
- Exercise and NMN interventions reduced adiposity and showed modest improvement in glucose tolerance and markers of mitochondrial function.
- NMN appeared to have stronger effects on liver fat catabolism and synthesis compared to exercise.
- The interventions were most effective in mice that were most metabolically challenged (HFD-consuming offspring of obese mothers).
- Further study is needed to confirm the suitability of NMN for reversing metabolic dysfunction caused by maternal obesity.
Maternal Obesity and Offspring Health:
- In the last three decades, the proportion of adults with a body mass index (BMI) greater than 25 has increased globally.
- Maternal obesity is associated with increased birth weight, adiposity, and the risk of offspring developing obesity.
- Developmental programming, shared environment, and genetics contribute to the association.
- Childhood obesity increases the risk of metabolic disorders later in life.
- Maternal obesity perpetuates the intergenerational cycle of obesity.
- Lifestyle interventions in the mother can reduce weight, triglycerides, and insulin resistance in offspring.
- Exercise during gestation protects against hepatic steatosis and glucose intolerance.
- Pharmacological therapies in obese mothers have shown successful outcomes for offspring.
- Interventions in the offspring themselves are still necessary.
- Mitochondria play a critical role in obesity-related diseases and the mentioned interventions.
- NAD+ levels are reduced in obesity and type 2 diabetes.
- Physical activity increases NAD+ levels and improves mitochondrial function.
- NAD+ precursors, such as NMN, are therapeutic targets for metabolic disorders and aging.
- NMN supplementation increases NAD+ levels and improves metabolism in various conditions.
Investigating the Effects of NMN Supplementation on Offspring:
- Maternal obesity affects offspring adiposity and involves alterations to oocyte state and the gestational milieu.
- It is unknown whether NMN supplementation can reverse metabolic deficits initiated prior to birth.
- The study aims to test NMN administration in female offspring consuming regular or high-fat diet after weaning.
- The effects of exercise and NMN supplementation in female offspring will be compared.
- Weight gain, adiposity, glucose tolerance, mitochondrial DNA copy number, triglyceride levels, liver NAD+ and NADH levels, citrate synthase activity, and mRNA levels of fat metabolism markers will be measured.
Experimental Protocol and Results:
- Female mice were used in the experiment.
- Mice were acclimatized to the diets before being assigned to control or HFD groups.
- Pregnant mice were housed individually, and their diets were continued throughout pregnancy and lactation.
- Offspring were weaned and distributed across the diet groups.
- After post-weaning diet, offspring from HFD-fed mothers were further distributed into sedentary, exercise, or NMN groups.
- Glucose tolerance tests were performed, samples were collected, and various measurements were conducted.
- Maternal HFD increased pup body weight prior to weaning.
- Maternal obesity and offspring HFD consumption had significant effects on body weight, organ weights, glucose tolerance, insulin levels, liver triglycerides, and gene expression.
- Maternal obesity was associated with reduced NAD+ concentrations, but NMN supplementation increased NAD+ levels.
- NMN and exercise reduced body weight and fat accumulation, with stronger effects in offspring consuming HFD.
- NMN increased mitochondrial activity and beta-oxidation, reduced fat synthesis, and decreased fatty acid import.
- Both NMN and exercise partially improved glucose tolerance and increased plasma insulin levels in offspring with post-weaning HFD.
- NMN supplementation and exercise had similar effects in a mouse model of maternal obesity.
- The interventions were most beneficial in the metabolically challenged offspring consuming HFD.
Conclusion:
- Maternal obesity during pregnancy can have long-term health risks for offspring.
- Strategies like exercise and NMN supplementation can improve metabolism.
- NMN treatment showed promising results in reversing negative effects of maternal obesity on offspring.
- Further research is needed to explore the potential of NMN as a therapeutic option.
Title of paper: Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise
Author(s): Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ.
Year published: 2017
Published in: Sci Rep
Original article can be found here.
