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An essential regulator of body weight revealed

Scientists are one step closer to unraveling the complex mechanisms in the brain that regulate body weight. Working with mice -- whose appetites are controlled by systems very similar to those in humans they have identified a specific type of neuron that is essential for feeding behavior. Without these neurons, adult mice stop eating and undergo rapid weight loss.

Remarkably, the researchers found that absence of these neurons only influenced eating behavior when they were removed from adult mice. If the neurons were eliminated in newborn mice, their developing brains found a way to compensate for the deficiency, and the mice grew up eating normally. The research, conducted by Serge Luquet at the University of Washington in the laboratory of Howard Hughes Medical Institute investigator Richard D. Palmiter, will be published in the October 28, 2005 issue of the journal Science.

The task of sorting out the body's diverse and sometimes conflicting signals about hunger and satiety falls to a small cluster of about 5,000 cells in a region of the brain known as the arcuate nucleus. Hormones such as insulin, leptin, and ghrelin deliver information to the arcuate nucleus about whether the body has sufficient calories and nutrients. The brain, in turn, uses this information to decide whether to eat or expend energy.

Two types of neurons that recognize and respond to these signals are found in the arcuate nucleus. The first of these, known as POMC (pro-opiomelanocortin) neurons, send signals to other parts of the brain to reduce appetite. Mice with defects in POMC neurons eat excessively and become obese.

The other neurons that make up the arcuate nucleus are NPY/AgRP neurons, named for two proteins they produce, neuropeptide Y (NPY) and agouti-related protein (AgRP). Researchers have long suspected NPY/AgRP neurons to be important regulators of feeding behavior, acting in opposition to POMC neurons to stimulate appetite. But genetic
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Contact: Jennifer Michalowski
michalow@hhmi.org
Howard Hughes Medical Institute
27-Oct-2005


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