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Environmental Factor, December 2015

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Simmons speaks on the origins of obesity

By Virginia Guidry

Rebecca Simmons

“For public health policy, we need to think about counseling girls at a young age to pay attention to their weight, because their weight as it occurs during and after puberty appears to have a profound influence, independent of lifestyle factors, on their offspring,” said Simmons. (Photo courtesy of Steve McCaw)

Jerry Heindal

Heindel noted that Simmons’ research is related to the second goal of the NIEHS strategic plan, regarding key windows of susceptibility to environmental factors. “Her presentation and visits with staff will help us consider potential research funding in these areas,” he said. (Photo courtesy of Steve McCaw)

The tendency toward obesity may originate before conception, according to research that Rebecca Simmons, M.D., presented in an Oct. 26 seminar.

“We invited Dr. Simmons to speak because of her expertise in many priority areas for NIEHS, including the developmental origins of adult disease, epigenetics, and obesity,” said Jerry Heindel, Ph.D., NIEHS health scientist administrator and host of the talk. Simmons’ talk, “Programming of Obesity for Life: Is It Over Before Conception?” was part of the Keystone Science Lecture Seminar Series.

According to Simmons, a professor at the Perelman School of Medicine at the University of Pennsylvania, 66 percent of women of reproductive age are overweight and 35 percent are obese. Obesity has been linked to abnormalities in reproduction, such as difficulty getting pregnant, increased rate of miscarriages, and smaller babies than normal. She also cited research showing that obese parents are more likely to have obese children. Simmons and her group are studying when the tendency toward obesity begins.

Metabolic changes passed to offspring

Simmons’ team showed that mice fed a higher carbohydrate, higher fat Western diet became visibly obese and had abnormal metabolic functioning at the cellular level. The abnormal metabolic profiles observed by the researchers suggested that the diet, which was started immediately after puberty in the mice, triggered oxidative stress and inflammation.

Importantly, the scientists also found that these metabolic changes could be passed down to offspring. The team used metabolomics studies to look at the biochemical differences between Western diet and control diet groups. When mice that were obese from eating the Western diet became pregnant, their embryos showed the same altered biochemical profiles, predisposing the offspring to obesity.

Preconception environment influences obesity

In their next series of experiments, Simmons’ lab found that the tendency toward obesity is influenced by the maternal environment before conception and the environment in the womb.

The scientists saw differences between obese and normal weight mice at several developmental stages. There were noticeable deficiencies in the placentas of obese mice, even very early in pregnancy. They also found that oocytes, or eggs, from obese mice were of lower quality than those from control mice. This has been established by other research, but Simmons’ lab demonstrated the presence of important genetic and epigenetic differences that contributed to these changes and enabled them to be passed down to offspring.

“There are multiple windows of exposure that affect developmental programming of adult disease, and these intersect and interact,” Simmons said in summary. “The pregestational environment, the preconception environment, the gestational environment, as well as a period of time during lactation, all interact to produce obesity-related changes in the offspring. It is very important now to recognize that these windows have been pushed back to include preconception.”

(Virginia Guidry, Ph.D., is a technical writer and public information specialist in the NIEHS Office of Communications and Public Liaison.)

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