Vidyya Medical News Service
Volume 6 Issue 176 Published - 14:00 UTC 08:00 EST 24-Jun-2004 Next Update - 14:00 UTC 08:00 EST 25-Jun-2004
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Evidence for fat hormone target in brain

Nina Balthasar and her colleagues have presented direct evidence that the fat hormone leptin affects a specific type of target neurons in the brain -- a prime link in the brain's regulation of the body's energy balance.

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.


Nina Balthasar, Roberto Coppari, Julie McMinn, Shun M. Liu, Charlotte E. Lee, Vinsee Tang, Christopher D. Kenny, Robert A. McGovern, Streamson C. Chua Jr., Joel K. Elmquist, and Bradford B. Lowell: "Leptin Receptor Signaling in POMC Neurons Is Required for Normal Body Weight Homeostasis"

Published in Neuron, Volume 42, Number 6, June 24, 2004.

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