Drug targets brain circuits that drive appetite and body weight

Research conducted in animals has revealed that an appetite suppressant drug, D-fenfluramine (D-FEN), activates brain pathways that regulate food intake and body weight. The NIH-funded study suggests that drugs targeting central nervous system pathways affecting appetite, obesity, and anorexia may lead to selective, effective treatments for weight control. Results appear in the July 26, 2002, Science.

A study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) found that anorexia induced by d-FEN in rodents activates melanocortin neurons in the central nervous system. The drug, once prescribed for losing weight and known as fen-phen when used with phentermine, was withdrawn by the Food and Drug Administration after reports of cardiac complications. The National Institute of Mental Health (NIMH) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) supported the research.

The scientists set out to identify ways that d-FEN, which increases the brain's release of serotonin, a neurotransmitter that relays nerve impulses and curbs appetite, boosts this effect. Using a dose of d-FEN that reduced feeding behavior, they correlated anorexic effects with activity patterns in a network of neurons in the brain. Researchers targeted the arcuate nucleus (ARC) region of the hypothalamus, where pro-opiomelanocortin (POMC) neurons receive serotonin directly and signal to regions associated with regulating energy.

"Our study has linked the serotonin system, a classic brain pathway thought to be involved with eating disorders like anorexia nervosa, to the melanocortin system, a brain pathway involved in obesity," explained the study's senior author, Joel Elmquist, D.V.M., Ph.D., a neuroscientist and endocrinologist at BIDMC and Associate Professor of Endocrinology and Medicine at Harvard Medical School.

Using electrophysiology studies of the hypothalamus in mice, scientists found that d-FEN doubles the fir

Contact: Constance Burr
NIH/National Institute of Mental Health

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