Metabolic Changes In Rats That Make Them Obese Later In Life Passed On to Offspring

BUFFALO, N.Y. -- Can changes in the diets of newborns that cause them to be obese later in life predispose their offspring to be obese as well?

At least in the case of female rats, the answer may be "yes," according to research conducted at the University at Buffalo.

The results, published in two papers in the October issue of the American Journal of Physiology, are the first to show that diet-induced metabolic adaptations in the early stages of a first generation were transmitted to a second generation, regardless of the type of diet the second generation was fed.

While other studies in this area have shown that total calories fed to newborns may have an effect later in life, the work by the UB researchers is the first to show that the distribution of those calories among major nutrients, such as fat and carbohydrates, also is significant.

"The implication of this research is that dietary experiences very early in life play a critical role in metabolism later on and on to the next generation," said Mulchand S. Patel, Ph.D., professor and chair in the UB Department of Biochemistry and co-author.

"If these phenomena also occur in humans, then diet-induced metabolic changes in obese parents may predispose their children to be obese, regardless of the kind of diet the children are fed," he said.

The UB researchers mated male and female rats that were fed a high-carbohydrate diet as newborns, and who subsequently became hyperinsulinemic (exhibiting higher than normal levels of insulin) and obese.

Progeny of these pairs became obese later in life, too, apparently because changes in the mother's metabolism were passed on to the fetus in the intrauterine environment. The researchers cautioned that there is no evidence that these changes are hereditary.

"This means that during the early stage of development, when cells were differentiating, this change was integrated in the systems of the progeny," said Patel.

"The mother is obese and hyperinsulinemic and somehow this information on altered maternal metabolism was transmitted to the progeny."

The researchers recently observed that progeny of parents in which only the male rats were fed the high-carbohydrate diet did not become obese.

However, progeny of parents in which only the female rats were fed the high-carbohydrate diet did become obese, indicating that the metabolic change in the progeny is contributed by the mother.

In a related paper published in the same issue of American Journal of Physiology, the researchers showed that the increase in insulin levels seen in the rats on the high-carbohydrate diets also occurred in their progeny.

Patel began studying the effects of dietary changes in newborn rats in the mid-'80s, when he was at Case Western Reserve University.

He co-authored the recent papers with Suzanne G. Laychock, professor of pharmacology and toxicology at UB, Satyaprasad Vadlamudi, postdoctoral associate at UB and Satish C. Kalhan, pediatrics professor at Case Western Reserve University.