Always hungry?
More leptin and fewer cannabinoids in the brain will curb your appetite.

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How to Stop the Munchies

Marijuana has a reputation for making people dash to the kitchen (or the nearest convenience store). New research shows why and helps explain how a hormone called leptin usually keeps the appetite under control. The results may help scientists design better diet drugs.

Researchers have known for several years that a connection exists between leptin and cannabinoids, the molecules in the brain that stimulate appetite and that are related to those found in marijuana (ScienceNOW, April 11 2001). Mice that don't make leptin have oversized appetites, for example, and they have unusually high concentrations of cannabinoids in the hypothalamus. But no one knew how leptin and cannabinoids interacted in the brain.

To examine the relation, Young-Hwan Jo, now at the Albert Einstein College of Medicine, New York City, and colleagues, took a look at slices of mouse hypothalamus. When the team dropped a cannabinoidlike compound onto the neurons, the neurons fired. If the researchers added leptin first, the neurons did not activate.

Both compounds seem to be exerting their influence via calcium ions. Cannabinoids increase calcium in the cell by opening pores, allowing the ion to enter the cell. So the researchers repeated their experiments while measuring calcium inside the activated neurons. Leptin stopped the pores from opening and thus prevented an influx of calcium. Separate experiments revealed that the brains of mice who don't make leptin have greater cannabinoid-induced influx of calcium into hypothalamic neurons than do the brains of mice who make leptin. Because cells require calcium to make cannabinoids, leptin helps keep appetite in check by making sure there aren't too many cannabinoids in the brain, the team reports 22 December in Neuron.

"This is a very important paper," says endocrinologist Uberto Pagotto of the Centro di Ricerca Biomedica Applicata, Sant Orsola-Malpighi Hospital, Bologna, Italy, who notes that the findings may help researchers develop better therapies for obesity.

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