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

BOSTON In investigating the complex neurocircuitry behind weight gain and glucose control, scientists have known that the hormone leptin plays a key role in the process. But within the myriad twists and turns of the brain's intricate landscape, the exact pathways that the hormone travels to exert its influence have remained a mystery.

Now, a study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) sheds further light on the subject. Reported in tomorrow's issue of the journal Cell Metabolism, the findings demonstrate that when leptin sensitivity is restored to a tiny area of POMC neurons in the brain's hypothalamus, a group of mice deficient in the leptin-receptor are cured of severe diabetes and also spontaneously double their activity levels independent of any change in weight or eating habits.

"This discovery suggests a new therapeutic pathway for drugs to treat insulin-resistant diabetes in humans with severe obesity, and possibly even to stimulate their urge to exercise," explains Christian Bjorbaek, PhD, an investigator in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Associate Professor of Medicine at Harvard Medical School. "We know that the majority of humans with Type 2 diabetes are obese and that weight loss can often ameliorate the disease. However, in many cases, it's difficult for these individuals to lose weight and can keep weight off. If, as these findings suggest, there is a system in the brain that can control blood-glucose directly, it offers hope for the identification of novel anti-diabetic drug targets."

First identified in 1994 as an appetite and weight-regulation hormone, leptin plays a key role in energy homeostasis through its effects on the central nervous system. Over the years, investigators have pinpointed a region of the brain's hypothalamus known as the arcuate nucleus (ARC) as one key area where leptin exerts its influence, and within the ARC, they h
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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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