French researchers have identified a protein that influences the body's sensitivity to leptin, the hormone that controls our body weight by letting us know when we have had enough to eat. The work, which is published online by the journal the Proceedings of the National Academy of Sciences (PNAS), could lead to the development of new treatments for obesity.

Leptin plays a key role in maintaining a healthy body weight by regulating food intake and energy expenditure. It works by triggering specific leptin receptors (OB-R) in the hypothalamic arcuate nucleus (ARC), the part of our brain responsible for controlling body weight.

The hormone is secreted by fat cells, and the level of leptin in the blood is proportional to the amount of fatty tissue in our bodies. In subjects with a healthy weight, high levels of leptin trigger an increase in energy expenditure and a decrease in appetite. This leads in turn to a decrease in the amount of fatty tissue and the amount of leptin circulating in the blood. However, in overweight and obese people, this system breaks down as the body becomes resistant to leptin, leading to further weight gain.

In 1997, scientists discovered that the gene which codes for the leptin receptor (OB-R) also codes for another protein, which they called OB-RGRP (OB-R gene related protein).

In this latest study, French scientists fed a high-fat diet to mice in which the production of OB-RGRP had been blocked. In spite of their unhealthy diet, the mice maintained a healthy body weight. The researchers found that OB-RGRP is responsible for the intercellular transport of the leptin receptor OB-R. Blocking the production of OB-RGRP led to an increase in the number of leptin receptors present on the cell surface, effectively rendering the cell more sensitive to leptin.

The scientists believe that inhibiting the production of OB-RGRP could restore the leptin-sensitivity of obese people and so help them to lose weight more easily.

"Our study provides interesting insights on regulatory mechanisms of BO-R signalling and shows that OB-RGRP is a promising therapeutic target for the treatment of obesity," the researchers write.

For more information, please visit:

• http://www.inserm.fr
• http://www.pnas.org

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