Leptin Has Powerful Effect On Reward Center In The Brain

Leptin, a hormone critical for normal food intake and metabolism, exerts a strong effect on appetite by acting in the mid-brain region as well as in the hypothalamus, according to a Yale School of Medicine study in Neuron.

"Finding that metabolic hormones directly regulate the ventral tegmental area (VTA) of the mid-brain has profound implications for how researchers view the integration of metabolic signals in the brain," said the senior author, Ralph DiLeone, assistant professor of psychiatry.

In this study the researchers demonstrated that leptin signaling, via its receptor, occurs in the dopamine neurons in the VTA and that it results in decreased activity of these neurons.

"Metabolic control over dopamine neuron function in the VTA is likely to have consequences for a broad range of behaviors and associated pathologies," DiLeone said. "These include obesity, drug addiction, and other impulsive behavior."

Leptin's effect in the hypothalamus has been well studied, but it was not known how the hormone affected activity in the VTA, which contains dopamine neurons that are important in modulating motivated behavior, addiction and reward.

Reducing the function of the leptin receptor in the VTA region resulted in animals that ate too much and were hypersensitive to highly palatable foods. "Interestingly, despite the increase in food intake, these animals did not gain weight, possibly as a result of increased activity that was also seen in the animals," DiLeone said.

Food intake is influenced by signals that travel from the body to the brain. Leptin is one of the molecules that signals the brain to modulate food intake. It is produced in fat cells and informs the brain of the metabolic state. If animals are missing leptin, or the leptin receptor, they eat too much and become severely obese.

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Co-authors include Jonathan Hommel, Richard Trinko, Robert Sears, Dan Georgescu, Jeremy Thurmon, Zong-Wu Liu, and Xiao-Bing Gao, of Yale, and Michela Marinelli of the Rosalind Franklin University of Medicine and Science in Chicago.

Neuron 51: (September 19, 2006)

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Leptin Has Powerful Effect On Reward Center In The Brain