A new study has used a mouse model to show that maternal obesity appears to affect the feeding behaviors of offspring through a tiny RNA molecule called miR-505-5p. This study expands on previous research that has indicated that in both humans and animals, maternal obesity leads to an increase in the risk of diabetes and obesity in their offspring. The findings have been reported in PLOS Biology.
The link between maternal obesity and an increased risk of metabolic disease in offspring appears to involve many genetic and environmental factors, but this research has also shown how obesity in moms might disrupt hypothalamic function in their children. The hypothalamus plays a crucial role in the regulation of appetite and satiety.
In this work, the investigators showed that obese mothers had offspring that carried abnormally high hypothalamic levels of the microRNA miR-505-5p throughout their lives, from the fetal stages in some cases and into adulthood. These mice tended to prefer foods that were high in fats, and they ate more.
The researchers also found that when obese mothers exercised during pregnancy, it mitigated the metabolic impacts of miR-505-5p, along with eating behaviors in offspring.
In a cell culture model, the researchers also triggered the activity of miR-505-5p in hypothalamic neurons by exposing the neurons to long-chain fatty acids and insulin; both of these molecules are found at unusually high levels in obese pregnant people.
The researchers determined that miR-505-5p helps control pathways that involve fatty acid uptake and metabolism. The high miR-505-5p levels seem to disrupt the ability of the brain to sense the intake of high fat foods.
Some genomic association studies have linked genes that are regulated by miR-505-5p to high body mass index. This work has identified a potential molecular mechanism underlying the connection between maternal obesity and metabolic disease risk in offspring.
"Importantly, we showed that moderate exercise, without weight loss, during pregnancies complicated by obesity prevented the changes to the baby's brain," noted the study authors.
Sources: Public Library of Sciences, PLOS Biology
