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Study further expands understanding of leptin's role in brain neurocircuitry
Date:6/2/2009

ave identified two types of leptin-responsive neurons, the Agouti-related peptide (AgRP) neurons, which stimulate appetite and the pro-opiomelanocortin (POMC) neurons, which curb appetite.

"Still other studies had indicated that, by way of the ARC, leptin also had a function in both blood-sugar control and in activity levels," notes Bjorbaek. "We hypothesized that, in both cases, the POMC neurons were involved."

To test their hypothesis, the scientists studied a group of leptin-receptor-deficient laboratory mice. "The animals were severely obese and profoundly diabetic," he explains. "Using Cre-Lox technology we were able to genetically and selectively re-express leptin receptors only in the POMC neurons. When leptin receptor activity was restored to just this very small group of neurons, the mice began eating about 30 percent fewer calories and lost a modest amount of weight." And, he adds, even more dramatically, the animals' blood sugar levels returned to normal independent of any change in weight or eating habits, and their activity levels spontaneously doubled.

While more research is needed to explain the mechanisms at play, it may be that the POMC neurons reduce blood glucose by regulating key organs such as the liver or muscle tissue. "Normally, the liver is critical for increasing glucose production between meals in order to provide fuel for the brain, while skeletal muscle is important for the removal of glucose from the blood immediately after a meal," he notes. In this case, however, the POMC neurons may be decreasing glucose release into the blood by the liver and/or increasing glucose uptake from the blood into muscle.

"The fact that normal glucose levels were restored independent of food or weight changes is important because it suggests that it is possible to normalize blood glucose even without weight loss," explains Bjorbaek. "Furthermore, our finding that the mice had greatly increased activity levels despite st
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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