Retrospectacle: A Neuroscience Blog

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, a protein in brain cells may act as a linchpin in the body's weight-regulating system. It seems to play a key role in signaling in regards to fat storage, sugar use, energy balance and weight.

The experiments were performed in 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. They zeroed in on SH2B1's 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.

Rui and his team have already shown that mice that lack the gene for SH2B1 become obese and diabetic. [Unrelated side note: a friend pointed out to me that obese mice are used as models when studying diabetes. There's that much of a strong correlation.] These mice are unable to respond to signals sent to the brain by leptin and insulin which would normally result in a decrease in appetite, food intake, and fat storage. In a nutshell, mice that don't have this gene get really fat, as their brain can't communicate to stop eating.

Rui also developed mice that made an excessive amount of SH2B1. These mice did not become obese or diabetic even after being fed a high-fat diet that would have resulted in obesity in normal mice. This suggests that an over-active signaling system mediated by SH2B1 might protect the body from excessive fat storage and from diabetes.

"Obesity, whether in mice or humans, is the product of an altered balance between energy intake and energy use. The imbalance is linked to alterations in leptin and insulin signaling that lead to excess weight gain and Type 2 diabetes, respectively," says Rui, an assistant professor of molecular and integrative physiology at U-M. "SH2B1 appears to play a key regulatory role in this system, through its direct influence on the processing of leptin and insulin signals in cells of the brain's hypothalamus."

Get the free full-text paper here.