Diabetes linked to diet of mother
Pregnant women have been urged to take extra care over their diet in light of new evidence that it affects an unborn child's risk of diabetes many decades later.
Scientists pinpointed a gene in rats that can be reprogrammed in the womb by an unbalanced diet.
The modification led offspring of protein-deficient mothers to develop type 2 diabetes, the most common form of the disease.
Researchers believe a similar effect is likely to occur in humans, possibly involving different aspects of diet.
Theoretically, the genetic changes induced by poor nutrition in the womb could be inherited and passed on to future generations.
Dr Susan Ozanne, from the Institute of Metabolic Science at Cambridge University, who co-led the research, said: "Having a healthy well-balanced diet is important at any time during your life.
"A healthy well-balanced diet is particularly important during pregnancy because of the impact on the baby long-term, and the potential impact on the grandchildren as well."
Processes that allow environmental factors, such as diet, to alter the activity of genes are known as "epigenetic" and are still not well understood.
They result in genes being chemically tagged or "marked" in ways that can permanently switch them on or off.
Evidence from animal studies and some research on human populations suggests that epigenetic effects can be transmitted from one generation to another.
One study of historical records from the northern Swedish village of Overkalix indicated that being undernourished in the womb or fed too well in early childhood could reduce the lifespan of grandchildren.
The new research is the first to trace epigenetic effects to a particular gene.
It was already known that dietary factors early in life, including before birth, can influence long-term metabolic health. But scientists are still trying to understand how these effects occur.
The Cambridge team, whose work is published in the journal Proceedings of the National Academy of Sciences, focused on a "master regulator" metabolism gene called Hnf4alpha.
The gene plays an important role both in the foetal development of the pancreas and the later production of insulin by "islet" cells in the organ.
Feeding mother rats a low-protein diet led to epigenetic alterations which reduced the activity of Hnf4alpha, decreasing the ability of the pancreas to produce insulin. This in turn caused the offspring to develop type 2 diabetes much later in life.
The early effects of diet exacerbated those of normal ageing, which also down-regulated the gene, the scientists found.
Since Hnf4alpha is highly conserved among different species they expect the same, or similar, effects to be seen in humans.
To see if this is true, the researchers have now embarked on a new study looking at DNA from pancreatic cells taken from dead road accident victims.
Dr Ozanne said: "Bad diet in humans is a very broad spectrum of differences in diet. We know ... that lots of different sub-optimal diet - whether it be too little protein, too much fat, too much simple carbohydrates - all of those certainly in animal models increase the risk of diabetes in the offspring. What we don't know at the moment is if they all impact through Hnf4alpha."
Co-author Dr Miguel Constancia, from the department of obstetrics and gynaecology at Cambridge University, said: "It is remarkable that maternal diet can mark our genes so they remember events in very early life. Our findings reveal a novel mechanism by which maternal diet and ageing interact through epigenetic processes to determine our risk of age-associated diseases."
He said that although there was evidence that epigenetic changes could be transmitted across generations it was "far too dangerous" to start speculating about how often this occurs.
Dr Constancia added that one day it might be possible to develop treatments that target epigenetic defects in genes, but such advances were a long way off.
The research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the British Heart Foundation (BHF).
Professor Jeremy Pearson, associate medical director of the BHF, said: "We already know that a healthy pregnancy is important in shaping a child's health, and their risk of heart disease as they grow up. The reasons why are not well understood, but this study in rats adds to the evidence that a mother's diet may sometimes alter the control of certain genes in her unborn child.
"It's no reason for expectant mothers to be unduly worried. This research doesn't change our advice that pregnant women should try to eat a healthy, balanced diet."
Professor Douglas Kell, chief executive of the BBSRC, said: "Epigenetics is a relatively young field of research with tremendous potential to underpin our understanding of many biological processes in all organisms.
"This study ... shows us how apparently minor changes within cells at the very earliest stages of development can have a major influence on our health into old age."