UC Toxics News: Fall 2006
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"We think organotins can promote obesity through increased fat cell production." - TSR&TP investigator Felix Grun

Organotins are known as anti-fouling agents in paint for marine vessels, but they are also ubiquitous in our homes and offices. Organotins are chemical compounds used as heat stabilizers for polyvinylchloride or PVC, so they are found in our water supply piping, flooring, blinds, packaging, and toys. The constant low-level exposure to these known endocrine disruptors has led UC Irvine developmental and cell biology researcher Felix Grün to wonder if it may be linked to our increasing levels of obesity. Grün received a TSR&TP New Investigator Grant to explore his theory.

Grün did his doctoral research at Cornell University looking for new metabolites of Vitamin A (retinol). He began investigating endocrine disruptors as a cause for amphibian malformations when he joined Bruce Blumberg’s lab as a postdoctoral researcher at UC Irvine. They suspected vitamin A disruption could be the pathway. Grün began looking at chemicals in the water that have this activity, and organotins surfaced as a major group.

Organotins have been shown to activate the retinoid X receptor (RXR), the central receptor that regulates gene transcription in many signaling pathways, notably lipid and hormone homeostasis. By disturbing these pathways, RXR may affect how the body regulates fat stores. “We think these compounds can promote obesity through increased fat cell production,” explains Grün.

Newborn mouse fat deposits have accumulated excess lipid after developmental exposure to organotins. Cryosections were stained with hematoxylin and lipid content visualized with Oil Red O (red). Vehicle control only (left), tributyltin chloride exposed (right).

In studies Grün’s lab has conducted to date, if pregnant mice are exposed to organotins, the newborn mice will have increased lipids in their fat cells. Grün suspects the mice might also have an increase in their total number of fat cells, which would result in long-term effects. “Up to 10 weeks in age, the mice have the same type of growth curve as control animals,” explains Grün, “but at 10 weeks, we see a significant increase in fat deposits in the exposed mice.” The trend they are seeing is about a 10 percent increase in total body weight by the time a mouse is a year old. “If this were to hold true for humans, it would be about 20 pounds of extra fat in a 180-pound man,” says Grün, “That’s the difference between overweight and obese.”

Grün and his group are not claiming that all obesity is caused by organotins. “We really believe that diet and exercise are the overriding factors contributing to the obesity epidemic. We don’t know how these environmental obesogens contribute to make the problem worse, but even if it’s a minor factor, that’s significant.”

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