Tributyltin exposure may cause ‘transgenerational obesity’

By Helen Albert, Senior medwireNews Reporter

Research shows that offspring of mice exposed to low doses of the chemical tributyltin, used in paints, plastics, and other consumer products, have greater than normal body fat, liver fat, and fat-specific gene expression.

Remarkably, these mice then appear to pass this tendency toward obesity on to their offspring for at least two further generations without further exposure to the chemical, say the investigators.

Bruce Blumberg (University of California, Irvine, USA) and colleagues previously demonstrated that prenatal tributyltin exposure predisposes mesenchymal stem cells (MSCs) to become fat cells or adipocytes through epigenetic imprinting.

Building on their earlier research, the team exposed pregnant mice to placebo, the pharmaceutical obesogen rosiglitazone, or three doses of tributyltin (5.42 nM, 54.2 nM, and 542 nM) in their drinking water.

They then examined the offspring (F1) and two further generations of mice (F2 and F3) for signs of obesity and associated factors such as liver fat accumulation. The F1 animals were exposed to tributyltin in utero, the F2 animals were potentially exposed as F1 germ cells, and the F3 animals were not exposed.

The researchers found that adipocyte size and number increased significantly in the mice in the tributyltin group in all three generations compared with those in the placebo or rosiglitazone groups. In addition, white adipose tissue depot weights increased, as did the number of MSCs that became adipocytes rather than bone cells in these mice compared with in animals in the other two groups.

In addition, the mice in the tributyltin group, but not the other two groups, had increased liver fat accumulation and increased expression of genes associated with fat storage and regulation in all three generations.

Although these findings are in mice, Blumberg and colleagues believe that tributyltin may also be a human obesogen.

"If, as we expect, our model applies to humans, then prenatal obesogen exposure could permanently reprogram the metabolism of exposed individuals, predisposing them toward weight gain, particularly in conditions of caloric excess," they write in Environmental Health Perspectives.

"It should come as no surprise that chemical obesogens exist, because a variety of pharmaceutical drugs (e.g., tricyclic antidepressants, thiazolidinedione antidiabetic drugs, atypical antipsychotics) have been associated with weight gain in humans," they add. "These results show that early life obesogen exposure can have lasting effects."

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