University of Michigan Medical School researchers report that a single protein in brain cells plays a key role in controlling body weight, response to insulin// and leptin, and energy balance. Their research findings on a protein called SH2BI and its activity in brain cells were reported in the February issue of the Journal of Clinical Investigation.

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

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, U-M researcher Liangyou Rui, Ph.D. 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 didn’t have the SH2B1 gene, but also at mice that made SH2B1 only in brain cells, either in normal or larger-than-normal amounts. They found that restoring SH2B1 just in the brai
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