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Weight control protein may yield antiobesity drugs

A weight control protein with a key role in the brain's ability to monitor body fat content may yield new approaches for treating obesity and type 2 diabetes, according to a new report in the August issue of Cell Metabolism. The findings in mice further suggest that particular variants of the protein SH2-B might underlie obesity in humans, the researchers said.

SH2-B, which has multiple functions in cells throughout the body, keeps the brain sensitive to the fat hormone leptin, found researchers from the University of Michigan Medical School. Produced by fat tissue, the leptin hormone sends signals to the brain about the body's fat content. That signal, in turn, elicits adjustments in appetite and energy expenditure to maintain normal body weight.

Mice lacking SH2-B overeat and become obese, the team found. The animals additionally develop a metabolic syndrome characterized by high blood concentrations of leptin, insulin, and lipids. They also develop fatty livers and high blood sugar, the group reports.

"Our findings reveal SH2-B as an important positive regulator of leptin sensitivity inside cells of the brain region known as the hypothalamus," said senior author of the study, Liangyou Rui. The hypothalamus is a key area in the central nervous system that integrates neuronal, hormonal, and nutrient-related signals to maintain body weight, he explained.

Leptin is a hormone produced by fat that normally decreases food intake and increases energy expenditure. In many species, including humans, the hormone acts to stabilize weight and glucose balance through activating its receptors in the hypothalamus.

Earlier work by Rui's group found that SH2-B binds to a second protein, JAK2, to promote leptin signaling in cultured cells. Further work then identified a physiological role for SH2-B in the regulation of blood glucose; mice deficient for the protein develop insulin resistance and type 2 diabetes, they found.

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Source:Cell Press


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