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Major link in brain-obesity puzzle found

ANN ARBOR, Mich. A single protein in brain cells may act as a linchpin in the bodys weight-regulating system, playing a key role in the flurry of signals that govern fat storage, sugar use, energy balance and weight, University of Michigan Medical School researchers report.

And although its far too early to say how this protein could be useful in new strategies to fight the worlds epidemic of obesity, the finding gives scientists an important system to target in future research and the development of anti-obesity medications.

In the February issue of the Journal of Clinical Investigation, U-M researcher Liangyou Rui, Ph.D. and his team report their findings on a protein called SH2B1, and specifically on its activity in brain cells.

Using a variety of genetic, diet and hormone techniques, they were able to show that the action of SH2B1 regulates body weight, the action of the metabolic signaling molecules leptin and insulin, and the use of energy from food. It even moderated the impact of a high-fat diet on body weight.

The experiments were performed in mice, including two types of mice that the team altered genetically so that they only expressed a unique form of the SH2B1 protein in their brain cells. The protein occurs elsewhere in the body, but the researchers were able to zero in on its activity in the hypothalamus: the area of the brain that coordinates signals from the brain and body relating to food, hunger, and the balance of energy and nutrients in the body.

Previously, Rui and his team have shown that mice that lack the gene for SH2B1 -- called knockout mice -- become obese, diabetic, and unable to stop eating. Their bodies lose the ability to sense the signals sent by leptin and insulin that tell the brain to slow down food intake and fat storage.

For the new paper, they looked at not only normal mice and mice that didnt have the SH2B1 gene, but also at mice that made SH2B1 only in brain
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Contact: Kara Gavin
kegavin@umich.edu
734-764-2220
University of Michigan Health System
29-Jan-2007


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