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Environmental Chemicals—Not Just Overeating—May Cause Obesity
Obesity is a known risk factor for many cancers, and it is associated with an increased rate of some malignancies and the likelihood of aggressive disease in others. So new data showing that common environmental chemicals cause obesity in animal models may alarm some oncologists.
Until now, most physicians and researchers have thought that an imbalance of food intake and energy output—and a touch of genetics—is the root cause of obesity. But the cause may also link back to several hormone-altering chemicals. "When animals are exposed prenatally to these chemicals, their metabolism is reprogrammed so that even if they are never exposed again in their lives, they gain weight," said Bruce Blumberg, Ph.D., associate professor of developmental and cell biology at the University of California, Irvine. "Even with normal diet and normal exercise, they become obese.
"We think that is very relevant to the current epidemic of obesity," he said during a press conference devoted to chemicals and obesity at the American Association for the Advancement of Science meeting in San Francisco earlier this year.
The chemicals in question, which disrupt hormone system function in animals, are common in the human environment. Bisphenol A is used in polycarbonate plastics, including baby bottles and hard clear plastic water bottles, and for lining tin cans. Tributyltin has been used in the green paint on the underside of ships, which has led to ongoing seafood contamination with the chemical, and is a component of PVC (polyvinylchloride) plastic, a material sometimes used in household pipes.
When Frederick vom Saal, Ph.D., professor of biological sciences at the University of Missouri in Columbia, and colleagues exposed developing mouse embryos in utero to one dose of bisphenol A, the animals were born underweight relative to littermates that were not exposed. By 6 months of age, the exposed animals outweighed their siblings, despite being fed the same amount and type of food and having similar exercise habits.
"Not only are the animals getting heavy, they are forming cancers," vom Saal said. Interestingly, the level of chemicals the team used in these experiments is at or below the level found in human tissues, according to data from the Centers for Disease Control and Prevention.
Blumberg, vom Saal, and others are working out just how the reprogramming happens. While the details are still unclear, the changes appear to occur at the level of epigenetic alterations during development. Blumberg's team found that the chemicals activate the fat cell differentiation pathway in cells grown in vitro and in animal studies, which leads to both larger fat cells and more of them.
Thus far there are only correlative data suggesting that the chemicals are affecting human weight. Vom Saal, for example, cited a small Japanese study in which researchers found that women with a higher level of such chemicals tended to be heavier than those with lower levels.
The effect of similar endocrine-disrupting chemicals on adult animal health appears to be less permanent, according to at least some studies. The animals put on excess weight shortly after exposure but lose the weight again if the environmental source is withdrawn.
But if the researchers are correct that the chemicals are reprogramming human metabolism to favor weight gain, more cancers are likely to follow. "Unless the obesity from these chemicals is somehow different biologically from obesity as we understand it now, which I doubt, then it will be a concern," said Scott Lippman, M.D., chair of the department of clinical cancer prevention at the University of Texas M. D. Anderson Cancer Center in Houston.
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