Duke Study Suggests New Class Of Drugs Could Bypass L...( DURHAM N.C. -- Animal studies at Duke ...),Health

DURHAM, N.C. -- Animal studies at Duke University Medical Center show that the protein
leptin's role in weight loss has as much to do with burning stored fat reserves as it does with
signaling the brain that the stomach is full -- a discovery that could lead to a new class of drugs that
bypass the leptin brain circuit and target the fat cell itself.

Duke researchers say their study, reported today in the journal Nature, is the first to
demonstrate how leptin initiates the burning of stored fat, a process that has been postulated but never proven. In fact, their study shows that leptin is only the first step in a series of events that ultimately boosts fat metabolism, according to study authors Sheila Collins and Richard Surwit.

Leptin was identified last year as a protein that regulates body weight via appetite
suppression. But the complex circuit by which leptin begins the weight loss cycle is defective in
some obese animals and likely in obese humans, researchers found -- a theory confirmed by studies
showing that obese humans have elevated leptin levels yet remain obese. Researchers around the
country theorize that leptin remains elevated because the fat cells never receive its "slimming"
signal.

In studying the leptin loop, Duke researchers discovered they could apply a hormone -- a
synthetic form of noradrenaline -- directly onto the surface of fat cells, essentially bypassing the
leptin circuit. Receptors on the fat cell's surface, called B3 adrenergic receptors, receive the hormone's signal and transmit it inside the cell. The signal initiates a chain of events that results in the burning of stored fat.

Specifically, mice on a high-fat diet that received the synthetic noradrenaline stayed as slim as mice on a low-fat diet that received no noradrenaline. Results of this study were reported April 19 in the Journal of Biological Chemistry.

"Our results suggest that a cla
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Contact: Rebecca Levine
levin005@mc.duke.edu
919-684-4148
Duke University
29-Apr-1996


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