Maternal obesity can have a lasting impact on the eating behaviors of offspring through the long-term overexpression of the microRNA miR-505-5p, according to a new study published in the open-access journal PLOS Biology. The research, led by Laura Dearden and Susan Ozanne from the MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, UK, and colleagues, sheds light on the molecular mechanisms that link maternal obesity to increased risk of obesity and type 2 diabetes in offspring.
The study found that mice born from obese mothers had higher levels of miR-505-5p in their hypothalamus—the region of the brain responsible for nutrition sensing and energy homeostasis—from as early as the fetal stage into adulthood. These mice exhibited increased food intake and a preference for high-fat foods. Remarkably, the effect of maternal obesity on miR-505-5p and eating behaviors was mitigated if the mothers exercised during pregnancy.
Fatty Acids and Insulin Induce MiR-505-5p Expression
Cell culture experiments revealed that miR-505-5p expression could be induced by exposing hypothalamic neurons to long-chain fatty acids and insulin, both of which are elevated in pregnancies complicated by obesity. The researchers identified miR-505-5p as a novel regulator of pathways involved in fatty acid uptake and metabolism, suggesting that high levels of the miRNA may impair the offspring brain’s ability to sense when eating high-fat foods.
Several of the genes regulated by miR-505-5p have been associated with high body mass index in human genetic studies, further supporting the relevance of these findings to human health. The study is one of the first to demonstrate the molecular mechanism linking nutritional exposure in utero to eating behavior later in life.
Moderate Exercise During Pregnancy May Mitigate Effects
The authors emphasize the importance of their findings, stating, “Our results show that obesity during pregnancy causes changes to the baby’s brain that makes them eat more high fat food in adulthood and more likely to develop obesity. Importantly we showed that moderate exercise, without weight loss, during pregnancies complicated by obesity prevented the changes to the baby’s brain. This helps us understand why the children of mothers living with obesity are more likely to become obese themselves, with early life exposures, genetics and current environment all being contributing factors.”
The study highlights the complex relationship between maternal obesity and offspring health, with genetics, early life exposures, and current environment all playing a role. The findings suggest that moderate exercise during pregnancy, even without significant weight loss, may help mitigate the effects of maternal obesity on offspring eating behaviors and reduce their risk of developing obesity later in life.
As the global obesity epidemic continues to grow, understanding the molecular mechanisms that link maternal health to offspring outcomes becomes increasingly crucial. By identifying key players like miR-505-5p and the pathways they regulate, researchers can develop targeted interventions to break the intergenerational cycle of obesity and improve health outcomes for future generations.
