You Are What Your Great-Grandmother Ate? Transmission of Obesity Across Generations

Sarah Howard
Coordinator of CHE’s Diabetes-Obesity Spectrum Working Group

Two important studies have been published this month on chemical exposures that cause obesity in subsequent generations of rodents, long after the exposure ends. Until now, no prior studies on transgenerational obesogen exposures had been published. The results are alarming.

In the first study, pregnant mice (F0 generation) were exposed to low doses of the known obesogen tributyltin (TBT) and bred for 3 generations (up to the F3 generation). Thus, the F0 generation was exposed directly, the F1 generation exposed in the womb, the F2 generationsl could have been primordially exposed as germ cells in the developing fetus, and the F3 generation was not exposed directly (changes in the F3 generation are considered truly transgenerational). The TBT exposure had obesity-promoting effects on fat deposition on the F1 through the F3 generation, including increasing the number of fat cells, fat cell size, fatty tissue weights, and fatty livers (similar to non-alcoholic fatty liver disease (NAFLD) in humans). Interestingly, TBT exposure reprogrammed stem cells to develop into fat cells instead of bone cells.

The study, entitled “Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal obesogen tributyltin in mice”, was written by Raquel Chamorro-García, Margaret Sahu, Rachelle J. Abbey, Jhyme Laude, Nhieu Pham, and Bruce Blumberg, of the University of California, Irvine.

In the second study, pregnant rats (F0 generation) were exposed to a mixture of BPA and phthalates (both potential obesogens) of two different doses (both higher than comparable human exposure levels), which were then bred for three generations (up to F3). Researchers found a variety of effects in the F3 generation, including obesity (measured by body weight), pubertal anomalies, ovarian disease, and testicular disease (among others). Curiously, unlike the other abnormalities, obesity did not appear until the F3 generation, in males or females. Obesity was more severe in the animals whose great-grandmothers had been exposed to the lower doses of chemicals as compared to the higher doses. Interestingly, the F3 generation females developed both obesity and polycystic ovarian disease, which are associated with each other in humans as well.

The study, entitled “Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations”, was written by Mohan Manikkam, Rebecca Tracey, Carlos Guerrero-Bosagna, and Michael K. Skinner of the Center for Reproductive Biology, School of Biological Sciences, at  Washington State University.

While these studies examined obesity and other diseases, previous studies have found transgenerational effects of environmental chemicals on even more health endpoints in rodents, including kidney disease, prostate disease, tumors, decreased fertility, immune system effects, and more. What are the human implications of these studies? We do not know yet. But they do provide one more reason to prevent exposure to endocrine disrupting chemicals.

References

Both articles are available free online:
Chamorro-García R, Sahu M, Abbey RJ, Laude J, Pham N, Blumberg B. Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal obesogen tributyltin in mice. Environ Health Perspect (): .doi:10.1289/ehp.1205701.

Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK. 2013. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS.One. 8(1):e55387.

Recent news articles relating to this topic

BBC: Chemical defects ‘last generations’

Living on Earth: Chemicals that promote obesity down the generations

New York Times: Warnings from a flabby mouse

Science News: News in Brief: Chemical tied to intergenerational obesity

Los Angeles Times: How to make a fat mouse

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