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Identification of Brain Cells That Drive Binge Eating and Weight Gain

Researchers have identified a group of brain cells (referred to here as ZI-GABA cells) that, upon activation, induces rapid binge eating and weight gain in mice. Previous studies have shown that humans who receive brain stimulation of the region including these cells, as a form of therapy to treat neurological disorders, can develop compulsive eating habits. However, it was not clear why this treatment would elicit such a response.

To determine the role ZI-GABA cells play in eating behavior and body weight regulation, investigators used a technique that allowed them to use a light source to selectively control brain cells in mice that had been genetically modified to have light-responsive proteins on the surface of these cells. When they activated the ZI-GABA cells in these mice with laser light, the mice rapidly consumed large quantities of food compared to mice without light-activated proteins. Because previous observations have shown that ZI-GABA cells project (extend long fibers) into an area of the brain that may help regulate feeding, they investigated whether this area is a critical target for ZI-GABA cell control of food intake. Upon light stimulation, they found that ZI-GABA cells sent signals to cells in this target area that reduced their activity, subsequently inducing food foraging behavior, and dramatically increasing food intake. To assess whether activation of the ZI-GABA pathway leads to weight gain, they selectively light-stimulated the cells several times per day over the course of two weeks. Repeated activation led to increased feeding and weight gain in mice, both of which were significantly reduced when the light stimulus was removed. Consistent with the notion that mice resume normal feeding behavior and body weight in the absence of ZI-GABA activation, the researchers then selectively deleted ZI-GABA cells from a group of mice and found that these mice reduced their food intake and gained less weight.

Finally, the researchers explored the idea that, because ZI-GABA cells project an inhibitory signal to their target cells, in turn increasing feeding behavior, the target cells have an opposite effect on food intake. When they selectively activated the target cells, bypassing ZI-GABA, mice significantly reduced their food intake. Moreover, when they selectively eliminated the target cells, mice substantially increased feeding and body weight.

Taken together, these data suggest that activation of a robust inhibitory pathway involving ZI-GABA brain cells is capable of evoking rapid binge eating episodes. With further research, knowledge gleaned from these and future results could lead to the development of novel treatment strategies for binge eating disorders in humans.

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