Weight Matters: Big and little mouse pups become obese adults

Being either overnourished or undernourished before birth can alter gene activity, leading to obesity during adulthood, a study in mice suggests. The researchers predict that this finding could lead to more-tailored treatments for obesity in people.

Some scientists have proposed that obesity and a variety of diseases result from the conditions in which fetuses develop. To determine whether fetal changes in gene activity could initiate obesity, Frederick vom Saal of the University of Missouri–Columbia and his colleagues removed a single ovary from female mice. When these mice became pregnant, the eight or so fetuses that typically occupy both tubes of the mothers’ uteruses crowded into a single tube.

Vessels that feed into both ends of each tube of a mouse uterus supply it with the mother’s blood. Therefore, in the experiment, fetuses stuffed into the middle of the single uterine tube received less nourishment than fetuses at either end did. Those at either end of the tube were unusually heavy at birth, and those in the center of the tube were unusually light. Fetuses located at intermediate positions were born at normal weights.

As the baby mice grew into adults, vom Saal’s team found that the normal-weight babies typically became normal-weight adults and that the big babies became obese adults. Babies born light quickly became just as heavy as the obese babies and kept that extra heft into adulthood, the researchers reported last week in San Francisco at the annual meeting of the American Association for the Advancement of Science.

When the researchers analyzed gene activity in fat samples from the adult obese mice, they found 435 genes that were more active in one of the groups of obese mice than in the other. In most cases, these genes controlled metabolic activities, such as creating fat cells or regulating the cells’ uptake of energy-storing lipid molecules.

The results suggest that the amount of nutrition that the fetuses received permanently affected how their genes functioned, vom Saal notes. However, he adds that differing gene activity between the low– and high–birthweight groups suggests that their obesity stemmed from separate mechanisms, which haven’t been mapped out.

“To really understand a person’s obesity, we might have to go back in time to see how their genes were originally programmed,” vom Saal says. Once researchers pinpoint a person’s cause of obesity, they may be able to design a specific treatment.

Retha Newbold of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., who studies how chemical exposures can influence obesity, notes that vom Saal’s work strengthens the link that previous studies have found between fetal environment and disease. “It may not be that we are all just what we eat and what we burn. Our exposures during development may be playing a role in how we develop obesity,” she says.

From the Nature Index

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