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OHSU Researchers Locate and Study Key Cells in the Brain Involved in Body Weight Regulation

   Portland, Ore.

Research results printed in this week's edition of Nature

Researchers at Oregon Health & Science University have used a mouse model to successfully locate, mark and study a set of cells in the brain connected to one of the country's biggest health threats -- obesity. The work is printed in the May 24 edition of the journal Nature. Malcolm Low, M.D., Ph.D., and Roger Cone, Ph.D., at OHSU's Vollum Institute conducted this research in collaboration with researchers at Yale Medical School and the University of Buenos Aires.

The nerve cells, called proopiomelanocortin (POMC) neurons, are located in the hypothalamus of the brain. In addition to locating and marking these important cells, this research helps explain the fundamental role of a hormone called leptin on weight loss and weight gain. It is believed that this basic research in a mouse will help explain the reasons behind weight problems in humans. The work might provide information for the development of agents to combat obesity, which affects 40 million American adults, or wasting diseases where people have trouble gaining weight.

For years, scientists have theorized that leptin's effect on POMC neurons in the hypothalamus is one of the first steps of signaling in the brain that can lead to weight regulation. Normally, the hormone causes secretion of melanocortin, a small protein transmitter that triggers a reduction in feeding.

"Past research has shown that leptin-deficiency is linked to obesity," said Low, a scientist at OHSU's Vollum Institute and senior author of the research paper. "Most commonly, however, individuals with obesity have elevated leptin levels suggesting that they have developed a resistance to the effects of the hormone. While past research has provided information about the impacts of leptin on the hypothalamus of whole animals, little is known about the hormone's specific actions on the POMC neurons."

The researchers marked these neurons by fusing a gene normally expressed in the cells with a second gene that makes a brightly fluorescing protein. Low's group created transgenic mice with the fluorescent neurons. Michael Cowley, Ph.D., a research assistant professor in Cone's lab and first author of the paper, then characterized the electrical properties of the neurons.

"There are about 100 billion neurons in the brain, but only around 3,000 of these POMC cells regulating body weight. This new technique truly lets us find the needle in the haystack," said Cowley.

With a greater understanding of this complex system, scientists at OHSU hope to learn more about the cellular mechanisms behind appetite and obesity so that new treatment options may be available in the future.

The National Institutes of Health and the Fogarty International Center funded this research.


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