Leptin is known to be produced by the body's fat tissues and to signal brain cells to reduce appetite and food intake and increase energy expenditures. Although researchers had produced indirect evidence that leptin affects the activity of particular neurons called POMC neurons in the brain, there had been no direct evidence of such an effect. The POMC neurons are found in the brain's hypothalamus, believed to be an important region for regulating the body's energy balance.

To directly demonstrate such an effect of leptin, Balthasar and her colleagues constructed a mutant mouse in which they could selectively knock out the receptors for leptin on the surface of POMC neurons. When they tested the effect of eliminating the receptors, they found that the mice had significantly increased body weight, due to an increase in fat mass.

Surprisingly, however, the researchers found that the mice gained less weight than would be expected if POMC neurons were the only targets of leptin. The researchers theorize that the reduction of POMC neuron activity due to lack of leptin signaling triggers compensatory mechanisms that reduce the impact on the animals' weight and energy metabolism. The researchers theorized that leptin might act to inhibit other neurons that, in turn, normally inhibit POMC neurons, thereby enhancing POMC activity.

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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
23-Jun-2004