Rat studies show what mom eats may predispose offspring to diabetes, obesity
GAINESVILLE, Fla. — You are what your mom ate.
That could someday prove to be the latest twist on a well-worn adage, say University of Florida researchers who are scrutinizing basic biologic mechanisms to better understand whether fetal nutrition plays a role in the origin of certain diseases that surface in adulthood.
As alarm rises over soaring rates of obesity, diabetes and high blood pressure, scientists are eager to determine whether nature or nurture — or some combination — spurs development of these conditions.
“There are many people around the world who don’t have enough protein in their diets, and malnutrition is a major cause of babies being born small around the world,” said Donald Novak, M.D., a professor with the division of pediatric gastroenterology at UF’s College of Medicine. “There is a lot of evidence that when infants are born small, compared to their counterparts, they have a higher risk of these specific disorders. We are trying to sort out why that might be.”
One possible answer: What mothers eat when they are pregnant could alter the function of key genes in their offspring, even without changing the genes’ fundamental DNA sequence. The notion is part of a new field known as epigenetics.
This Sunday, at the annual meeting of the Pediatric Academies Societies in Washington, D.C., UF researchers are releasing preliminary findings from ongoing animal studies that reveal a high-protein maternal diet predisposes offspring to health problems such as insulin resistance in adulthood, a precursor to diabetes. Other early findings, published in the conference proceedings, show that protein deprivation during pregnancy also is linked to the development of larger body type in rats — a tendency that persisted for two generations.
The work of UF researchers and others also raises questions about standard care of premature babies and newborns whose growth in the womb was retarded. The suggested protein intake for these infants is relatively high, to help spur “catch-up” growth. In addition, babies who are fed formula tend to take in higher protein levels than those who are fed breast milk. But researchers don’t yet know what the long-term consequences of this increased protein intake might be, said Josef Neu, M.D., a professor of pediatrics in the division of neonatology at UF’s College of Medicine.
“Human babies who are fed their mother’s milk tend to get a lower protein intake than babies who are fed formula,” Neu said. “There is a higher incidence of obesity when the kids get older in the formula-fed babies. So it’s possible that there’s something about the composition of the formulas, like the protein composition, that causes obesity later on in life. Some of it might have something to do with the increase in type 2 diabetes that we’re seeing.
“It’s way too early to say anything definitive, but we have some suggestion that the animals that are fed a higher protein intake have more metabolic abnormalities when they’re adults,” he said. “We’re still in the process of doing these experiments and collecting more data.”
The notion that maternal diet may feed development of adult conditions such as metabolic syndrome is called the Barker hypothesis, for the English physician who noted a link between low birthweight and the development of the disorder, Neu said. Metabolic syndrome is a major public health problem characterized by a combination of abdominal obesity, high blood pressure and insulin resistance. UF researchers are among those specifically looking at how maternal diet might alter gene function and influence the transmission of disease to subsequent generations.
“You can modify genes without changing their basic structure by adding or subtracting small substances to them,” Novak said. “You can produce similar changes in the proteins that bind genes. Genes are tightly wound around proteins; if those proteins are altered in certain ways, it’s more difficult for the gene to be active or for new proteins to be made from the gene. We’re looking at changes in those areas.”
In one study, UF researchers fed one group of pregnant rats a low-protein diet and another group a normal diet. Their male and female offspring were then mated with normal rats; the pregnant females were fed a normal diet. Their offspring, in effect, the “grandchildren” of the rats originally fed a low-protein diet, weighed significantly more and tended to be less adept at handling alterations in blood sugar levels than rats whose “grandmothers” were fed a normal diet. The take-home message: nutrition during pregnancy influenced the health of rat offspring in adulthood — and also affected the health of future generations.
“The really exciting thing is that when these female rats mate and have their babies, the same thing begins to happen to their babies,” Neu said. “It’s a generational thing. The question is what the mechanism of this is. This is a part of the whole new very exciting area of epigenetics.”
In another study, researchers at UF, the University of Utah and the University Medical Center of Nantes, France, found that rats that received a high-protein diet during infancy showed signs of insulin resistance in adulthood, which is associated with the development of type 2 diabetes.
“These findings, while preliminary, point to areas which require further investigation,” Novak said. “Specifically, the mechanisms by which dietary intake alters both the modification and expression of genes, the ‘critical periods’ during pregnancy and early life during which these modifications may occur, and the mechanisms by which such changes are propagated from generation to generation are critical issues if effective therapies are to be defined.”