“The body is extremely efficient at controlling energy balance,” says Seeley, a professor in UC’s internal medicine department and recipient of the 2009 Outstanding Scientific Achievement Award from the American Diabetes Association.

“Think of fat tissue like a bathtub,” he says. “To keep the amount of water the same, you have to make sure that the speed of the water coming in and the water going out match. If the water is coming in faster than the water is going out, eventually you have to build a bigger bathtub.

“Obesity is the same. People who eat more calories than they burn have to build a bigger fat tissue ‘bathtub,’ and building new blood vessels is crucial to building this bigger bathtub. For each additional pound of fat tissue, you need to build a mile of blood vessels.

“What we found is that if we can target these fat tissue blood vessels, animals eat less and lose weight as their ‘bathtubs’ get smaller.”

Seeley and his team treated lean and obese mice and rats with the proapoptotic peptide for periods of four or 27 days. They measured energy intake and expenditure daily in all animals — some on low-fat diets, others on high-fat diets. The team found that the peptide completely reversed high-fat-diet-induced obesity in already obese mice and also reduced body weight in the mice and rats placed on high-fat diets. No changes were recorded in animals on low-fat diets.

Seeley’s team found that fat loss was occurring without major changes to energy expenditure, but with reduced food intake. The authors noted that there were no signs of illness with this treatment and results were independent of the actions of the appetite-controlling hormone leptin.

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