Researchers have identified a new area of the brain that responds to the fat hormone leptin in regulating body weight and energy expenditure. They said that the region seems to be particularly important in enabling the body to resist weight gain from a high-fat diet.
Their discovery, they said, indicates that leptin acts on more brain areas than previously believed, to regulate body weight.
Leptin is secreted by fat tissue into the bloodstream, where it travels to the brain and other tissues. It acts on leptin receptors in areas of the hypothalamus to trigger fat loss and decreased appetite.
Bradford Lowell and his colleagues published their findings in mice in the January 19, 2006, issue of Neuron. They reported that an area called the ventromedial hypothalamus (VMH) is also important in leptin response, in addition to the area called the arcuate nucleus (ARC) of the hypothalamus, which is already known to be a target of leptin signaling.
Even though leptin was known to act on the neurons of the ARC, wrote the researchers, knocking out leptin receptors in those neurons caused only mild obesity in mice, compared to the effects of knocking out such receptors throughout the brain. Such findings, they said, hinted at the role of another region of the hypothalamus as a leptin target. The VMH constituted a good candidate for such a leptin target region because neurons there express leptin receptors, said the researchers. Also, they noted, destroying the VMH produces massive obesity in mice.
To explore the role of the VMH in leptin signaling, Lowell and his colleagues generated mice lacking leptin receptors only in specific neurons in the VMH. Electrophysiological studies of the VMH neurons in these altered mice showed that they were not triggered by leptin to fire, as were such neurons in normal mice.