Exercise During Pregnancy Normalizes Eating Habits in the Offspring and Reduces their Risk of Type 2 Diabetes

Maternal obesity affects the eating behavior of offspring through long-term overexpression of the microRNA miR-505-5p. This is according to a study by Laura Dearden and Susan Ozanne from the MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, UK, and colleagues, published in the open access journal PLOS Biology. Previous studies in humans and animal models have shown that the offspring of obese mothers have a higher risk of obesity and type 2 diabetes. While this relationship is likely the result of a complex relationship between genetics and environment, there is emerging evidence that maternal obesity may disrupt the hypothalamus – the region of the brain responsible for food perception and energy homeostasis.

Maternal Exercise During Pregnancy Improves Metabolic Health of the Offspring

In animal models, offspring exposed to overeating during key developmental stages eat more, but little is known about the molecular mechanisms that lead to these changes in eating behavior. In this study, the researchers found that mice born to obese mothers had higher levels of the microRNA miR-505-5p in their hypothalamus – starting in the fetal stage and continuing into adulthood. The researchers found that the mice ate more and showed a preference for high-fat foods. Interestingly, the effects of maternal obesity on miR-505-5p and eating behavior were attenuated when the mothers exercised during pregnancy.

Cell culture experiments showed that miR-505-5p expression could be induced by exposing hypothalamic neurons to long-chain fatty acids and insulin, both of which are high in pregnancies complicated by obesity. The researchers identified miR-505-5p as a novel regulator of signaling pathways involved in fatty acid uptake and metabolism, such that high levels of miRNA render the offspring’s brain unable to recognize the consumption of high-fat foods. Several of the genes that miR-505-5p regulates have been linked to high body mass index in human genetics studies. The study is one of the first to reveal the molecular mechanism linking food exposure in utero to eating behavior.

The results show that obesity during pregnancy causes changes in the baby’s brain that lead to eating more high-fat foods and being more likely to develop obesity in adulthood. Importantly, researchers have shown that moderate exercise without weight loss during pregnancies complicated by obesity prevents the changes in the baby’s brain. This helps to understand why the children of obese mothers are more likely to become obese themselves, with early life experiences, genetics and the current environment all being contributing factors.

One study has shown that maternal exercise during pregnancy improves the metabolic health of the offspring, even if the mother is obese or follows a high-fat diet. The mother’s physical activity triggers the placenta to release the key protein SOD3, which leads to a lower risk of diabetes for the offspring. The results of the study show the mechanisms behind this process.

Maternal Obesity and Diabetes Risk of the Child

Maternal obesity and type 2 diabetes are on the rise. More than 30% of all women of childbearing age in Western and Asian countries are classified as obese. By 2045, 630 million people are expected to be living with type 2 diabetes. Children born to obese mothers or mothers with type 2 diabetes have an increased risk of diabetes, even if they go on to lead healthy lives. “With the increase in maternal obesity, a worrying cycle is forming in which the risk of diabetes is passed down from generation to generation,” says Joji Kusuyama, assistant professor at Tohoku University’s Frontier Research Interdisciplinary Institute (FRIS) and lead author of the study. “Stopping this cycle is a critical and urgent medical problem.”

Previously, the group had shown that physical activity during pregnancy has enormous benefits for the metabolic health of the offspring. They demonstrated that SOD3 (supuroexide dismutase 3), which is produced in the placenta, plays a key role in transferring the benefits of maternal exercise to the offspring. Building on this, the team investigated how SOD3 prevents the negative effects of obesity from being transmitted from mother to child and found that SOD3 inhibits the abnormalities in glucose metabolism in the offspring caused by a high-fat diet.

Exercise Can Reverse the Effects of the Mother’s High-Fat Diet on the Offspring’s Metabolism

Histone methylation plays a fundamental role in epigenetic modification, i.e. heritable changes in DNA strands that do not affect the inherited base pairs. The methyl group (-CH3) attaches to an amino acid in the tail of histone proteins that coat DNA, sometimes activating gene expression, sometimes inhibiting it.When the mother eats a high-fat diet, histone H3 trimethylation H3K4me3 is reduced in the fetal liver, inhibiting the expression of genes for glucose metabolism. The researchers found that this is caused by two things. Reactive oxygen species (ROS) – oxygen in a reactivated and activated state that supports the body’s metabolism and cellular functions – are increased. At the same time, WDR82, a key protein that regulates histone methyltransferase, becomes oxidative and impairs protein function.

The harmful effects of a high-fat diet of the mother on the metabolism of the offspring are reversed by maternal exercise. Genetic manipulations showed that SOD3 in the placenta is essential for the protective effect of maternal exercise on the offspring. The study also highlighted the importance of exercise in reversing this effect. When the researchers introduced N-acetylcysteine (NAC), an antioxidant that boosts liver performance, into the fetal liver, it failed to reproduce the results of SOD3. This suggests that naturally produced SOD3, which is produced during exercise during pregnancy, is critical for the metabolic well-being of the offspring.

Given the simplicity and cost-effectiveness of exercise, encouraging mothers to exercise could help reduce the alarming rates of obesity and type 2 diabetes. The benefits of SOD3 may not be limited to metabolism. It is possible that this protein has other benefits for other organs of the child. Researchers are currently investigating the changes in placental tissue caused by SOD3, which may have lifelong positive effects on the child.