Mothers who consume a poor diet through pregnancy risk leaving their children less able to store fats correctly in later life, leading to a higher risk of diabetes, according to new research in rats.
The animal study – published in the journal Cell Death and Differentiation – reports new insights into why nutrition during early development in the womb permanently influences later health.
They noted that whilst it is well understood that poor maternal diet can increase the later risk of type 2 diabetes and coronary heart disease – but the molecular mechanisms underlying such effects are poorly defined.
Willis and her team have now found such a mechanism – revealing that the processes involved in fat distribution and storage are controlled by a molecule called miR-483-3p. They found that miR-483-3p was produced at higher levels in individuals who had experienced a poor diet in their mother's wombs than those who were better nourished – leading to the development of smaller fat cells that left offspring less able to store fats in adulthood.
"One of the ways that our bodies cope with a rich modern western diet is by storing excess calories in fat cells,” said Professor Anne Willis of the University of Leicester, UK – who co-led the study.
“When these cells aren't able to absorb the excess then fats get deposited in other places, like the liver, where they are much more dangerous and can lead to type 2 diabetes," she explained.
The research team said their findings will contribute to the understanding of fundamental biological processes, “but also have important implications for improving human health as programmed miRNAs represent potential markers of disease risk as well as providing targets of rational therapeutic intervention strategies.”
In the new study, the research team reported that when pregnant rats were fed low protein diets, their offspring had higher levels of miR-483-3p.
Willis explained that the higher levels of miR-483-3p led to them developing smaller fat cells and left them less able to store fats in adulthood. The then revealed that found that miR-483-3p works by suppressing a protein called GDF3.
As a result she explained that the rats were less likely to become fat when fed a high calorie diet, but were at a higher risk of developing diabetes.
In order to back up their findings, the research team then investigated the levels of miR-483-3p in humans born after poor maternal nutrition – finding that those born with a low birth weight had elevated levels of miR-483-3p and reduced levels of GDF3.
The team noted that people born with a low birth weight had 70% less GDF3 than those born at a normal weight.
“Our observation that the changes in miRNA expression in both rats and humans occur before the development of the metabolic phenotype suggests that they are causative and do not arise as a consequence of metabolic dysfunction,” explained the researchers.
Source: Cell Death and Differentiation
Published online ahead of print, doi: 10.1038/cdd.2011.183
“Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes”
Authors: D. Ferland-McCollough, D.S. Fernandez-Twinn, I.G. Cannell, H. David, M. Warner, et al