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Research points to potential obesity treatment

DENVER -- In 1999, Drs. Miles Brennan and Ute Hochgeschewender announced their finding that melanocyte-stimulating hormone (MSH) regulates the balance of fat storage and metabolism. In April, they received a patent on the use of MSH analogs -- chemicals that mimic MSH -- as potential treatments for obesity (U.S. Patent #6,716,810).

Brennan is an associate research professor at the Eleanor Roosevelt Institute at the University of Denver (ERI) and Hochgeschwender is an associate member of the Oklahoma Medical Research Foundation. Their research also suggests that MSH integrates fat and glucose metabolism in the periphery, or body. The scientists began by engineering mice missing the pro-opio melanocortin (POMC) gene. The mice, which had no MSH in their bloodstream, became obese because they stored all the fat they ate without metabolizing any of it.

"We were then able to reduce their weight by adding MSH back into the peripheral circulation," says Brennan. "There are MSH receptors in essentially all peripheral tissues, and we know that mice treated with MSH experience an increase in the level of free fatty acids in the bloodstream. What we think happens is that MSH causes the adipocytes, or fat cells, to release free fatty acids, while other cells are stimulated to remove them from the bloodstream and burn them. Essentially it's a way to mobilize your stored fat for current needs."

The animals experienced no apparent ill effects with the weight loss. "The MSH has the highest activity when you have the highest level of excess weight," Brennan explains. "As the animal approaches normal weight, the effect plateaus out -- this is not going to be the anorexic's drug of choice, because when there's no more stored fat, you can't change the balance. We think it's got significant potential for obesity therapies."

MSH research pioneer Victor Hruby, agrees. "It's clear that the POMC gene and its products are involved in additional ways that Miles
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Contact: Warren Smith
wasmith@du.edu
303-871-2660
University of Denver
11-May-2004


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