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Newswise — BOSTON – For eight months at the end of World War II, the Nazis blocked food supplies to the Netherlands, resulting in a famine known as the Dutch Hunger Winter. The human tragedy provided a natural experiment that revealed a surprising scientific insight. Babies born to women who carried them that winter demonstrated characteristics that made them different from their brothers and sisters born in times of more abundance. They showed distinct biological differences, such as higher body weights, higher cholesterol and higher rates of diabetes. What’s more, these children’s children also demonstrated these metabolic traits.

Now, a team of scientists at Joslin Diabetes Center have demonstrated in mice that the benefits of exercise may also span generations. The team made the novel discovery that grandmaternal exercise improved the glucose tolerance in adult male and female grand offspring as they age, even in the absence of any exercise interventions for the offspring or grand offspring. The scientists also observed that grandmaternal exercise was linked to decreased fat mass in grand offspring, regardless of whether the grandmothers ate a healthy diet or a diet high in fat. The team’s findings are published in the journal .

“Environmental exposures can start early in life and it is now well-recognized that maternal lifestyle can alter the uterine environment in ways that result in increased or decreased risk of disease transmission to offspring,” said Laurie J. Goodyear, PhD, senior investigator of Integrative Physiology and Metabolism, at Joslin Diabetes Center and also a professor of medicine at Harvard Medical School. “We determined that there are striking effects of maternal exercise on the metabolic health of grand offspring as they age. Our findings suggest that, in a mouse model, exercise during pregnancy may help prevent obesity and diabetes not just in offspring, but in grand offspring as well.”

To investigate the effects of grandmaternal diet and exercise on grand offspring, Goodyear and colleagues randomly assigned six-week-old female mice to cages either with or without exercise wheels. Half of each group were fed healthy chow diets, while half were fed high fat diets. This produced four possible grandmaternal conditions: active, chow-fed; active, high-fat-fed; sedentary chow-fed, or sedentary high-fat-fed.

Once the first-generation of pups were born and weaned, all were raised without exercise wheels and chow-fed, then bred with sedentary, chow-fed females from a different lineage. The second-generation were also all raised without exercise wheels and were chow-fed. In other words, after the grandmothers were treated with the exercise, there was never any treatment of the offspring or grandoffspring.

After studying the grand offspring for a year, the researchers observed that grandmaternal exercise was linked to decreased bodyweight and increased bone mineral density in second-generation male offspring independent of grandmaternal diet. Male and female second-generation from exercise trained grandmothers also demonstrated lower fat mass.

When the researchers performed glucose tolerance tests, they found that second-generation males and females from sedentary grandmothers showed worsening glucose tolerance with age. The grandoffspring from exercise trained grandmothers, however, did not have this age-related decline in glucose tolerance, having markedly better metabolic health compared to grandoffspring from sedentary grandmothers. Grandmaternal diets had little impact on glucose tolerance.

“While there has been growing evidence in recent years that maternal exercise can improve the metabolic health of first-generation offspring, remarkably, our current data demonstrate that maternal exercise has similarly robust effects to improve the metabolic health of second-generation, adult male and female offspring,” said first author Ana Alves-Wagner, PhD, a senior post-doctoral fellow in the Goodyear laboratory.  “Our work shows that exercise during pregnancy in mice can be an important tool to improve the metabolic health of multiple generations, and  – if translatable to humans  – could help to decrease obesity and diabetes worldwide.”

Co-authors included Joji Kusuyama, Pasquale Nigro, Krithika Ramachandran, Nathan Makarewicz and Michael F. Hirshman of Joslin Diabetes Center.

This work was supported by National Institutes of Health (R01 DK1010043, P30 DK036836); American Diabetes Assocation (1-17-PMF-009); research fellowships from Sunstar Foundation, JSPS Overseas Research Fellowships, Kanae Foundation, and Meihi Yasuda Life Foundation of Health and Welfare.

The authors declare no conflicts of interest relevant to this article.

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 About Joslin Diabetes Center

Joslin Diabetes Center is world-renowned for its deep expertise in diabetes treatment and research. Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and disseminate innovative patient therapies and scientific discoveries throughout the world. Joslin is an independent, non-profit institution affiliated with Harvard Medical School, and one of only 16 NIH-designated Diabetes Research Centers in the U.S.

Joslin Diabetes Center is a part of Beth Israel Lahey Health, a health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,800 physicians and 36,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.