Monday January 9 2012
Our time in the womb is though to greatly affect our future health
A bad diet during pregnancy raises an unborn child’s risk of developing diabetes in later life, The Daily Telegraph has reported. The newspaper said that a mother’s poorer diet in pregnancy reduces a person’s ability to store fat once they reach adulthood.
The news headlines are based on the results of a laboratory study that investigated how nutrition in early life could affect fat tissue. Researchers found that a molecule, called miRNA-483-3p, is present at increased levels in the fat of both men who had a low birth weight and rats whose mothers were fed a low-protein diet during pregnancy. The researchers also experimented with cells that have the ability to mature into fat cells (fat cell precursors). Exposing the cells to high levels of miRNA-483-3p in the laboratory reduced their ability to form fat cells and to store fats. The researchers propose that high levels of miRNA-483-3p cause fats to be stored in the liver and muscle, leading to insulin resistance and diseases including diabetes.
A healthy diet during pregnancy is sensible, and there is increasing evidence that exposure in early life to environmental factors such as poor nutrition has long-term effects on health. This study on cells in the laboratory has proposed a mechanism for how poor nutrition in early life may affect fat tissue and lead to increased risk of diabetes, but has limited direct relevance to humans.
Where did the story come from?
The study was carried out by researchers from the Medical Research Council’s Toxicology Unit and the University of Cambridge in the UK, Massachusetts Institute of Technology in the US, and the Steno Diabetes Centre in Denmark. It was funded by the Biotechnology and Biological Sciences Research Council. The study was published in the peer-reviewed journal Cell Death and Differentiation.
This study was covered by The Daily Telegraph and the Daily Mirror. Although the coverage was mainly accurate, the headlines suggested that the research was carried out in humans, whereas the study was mostly performed using rats and cells grown in the laboratory. In addition, the study focussed mainly on possible mechanisms for how poor nutrition could affect fat tissue, rather than maternal nutrition and diabetes risk.
What kind of research was this?
This laboratory-based study examined whether early nutrition affected the production of small molecules called microRNAs (miRNAs), and if miRNAs affect fat cells.
RNA has numerous functions in cells. One form of RNA, called messenger RNA (mRNA), is used to carry the information about proteins encoded in DNA to the parts of the cell that makes proteins. Particular forms of another type of RNA, called miRNA, can bind to specific mRNAs. When this occurs, it signals to the cell to degrade the mRNA. This results in reduced levels of specific proteins. In this way, the cell can control how much protein it makes.
The study initially identified a target miRNA in rats, which the researchers confirmed was present in humans. The function of the miRNA and how it might affect fat cells was then investigated in human and rodent cells grown in the laboratory.
This is the ideal experimental design to answer the researchers’ question, particularly as certain parts of the experiments would either be unethical or too difficult to perform on humans. However, applying the results of this lab work to humans requires caution. This is especially so as the human part of the study looked at young men with low birth weight, rather than young men whose mothers had had restricted diets during pregnancy. There are many reasons for low birth weight, which does not necessarily indicate a poor maternal diet.
What did the research involve?
The researchers initially performed their experiments on rats. They fed two groups of rats with either a low-protein diet (8% protein) or a control diet (20% protein) during pregnancy and lactation. Then, once the rats’ offspring were three weeks old, they were weaned onto a normal laboratory diet. The researchers compared the offspring’s levels of different miRNA molecules, glucose, insulin, fat and cholesterol, as well as body weight and body fat, at 22 days and 3 months.
The researchers then investigated whether young men who had been born with low birth weight also had higher levels of specific miRNAs. The researchers then looked for potential substances or processes that the miRNA might influence.
Further experiments were performed in laboratory-grown cells to confirm the effect of the miRNA and to see its effect on fat cells.
What were the basic results?
The offspring of rats fed a low-protein diet had reduced body weight and reduced body fat at three months of age compared with the offspring of rats fed the control diet. The researchers found that the fat cells of rats fed the low-protein diet were smaller. However, levels of glucose, insulin, fats and cholesterol were not significantly different.
The researchers identified that miRNA-483-3p was found at increased levels in the fat cells from the offspring of rats fed the low-protein diet. The same miRNA was present at increased levels in the fat cells of men of low birth weight, compared with men with normal birth weight. The researchers identified a protein called GDF3 as a potential target of miRNA-483-3p. They found that levels of this protein in fat were decreased by 40% in the offspring of mice fed the low-protein diet compared with offspring of mice fed the control diet. In humans, levels of this protein were decreased by 70% in the fat of men with low birth weight compared with men with normal birth weights.
The researchers confirmed that miRNA-483-3p directly regulated levels of the protein GDF3 in laboratory-grown cells. They found that miRNA-483-3p inhibited the formation of fat cells and the accumulation of fats.
How did the researchers interpret the results?
From their results and the results of earlier studies, the researchers proposed that increased miRNA-483-3p, caused by poor nutrition in early life, limits the storage of fats in fat cells. This causes fats to be stored in the liver and muscle, leading to insulin resistance and diseases including diabetes. They suggest that their results demonstrate that changes in miRNAs “contribute to the relationship between early-life nutrition and long-term health”, and have “important implications for improving human health as programmed miRNAs represent potential markers of disease risk”. They added that miRNAs are therefore targets for potential treatments in the future.
In this study, researchers found that a specific molecule (miRNA-483-3p) is present at increased levels in the fat of both the offspring of rats fed a low-protein diet and in men with a low birth weight. The researchers found that when fat cell precursors were exposed to increased levels of miRNA-483-3p in the laboratory, they showed a reduced ability to form fat cells and to store fats. The researchers demonstrated that at least part of this effect was due to reduced levels of the protein GDF3.
A healthy diet in pregnancy is sensible, and there is increasing evidence that exposure in early life to environmental factors such as poor nutrition has long-term effects. This study has proposed a mechanism for how poor nutrition in early life may affect fat tissue and lead to increased risk of diabetes, but has limited direct relevance to humans.