Subtype of Brain Cells May Lead to Novel Obesity Treatments

Activation of glutamine-releasing neurons in the brain stem resulted in lower food consumption.

For many patients, overeating and a lack of exercise are factors that drive the development of obesity. Despite the link between obesity and cancer, there seems to be a slow uptake in the development of novel drugs that treat obesity.

In a new study published by Cell, investigators discovered 2 new types of brain cells that may control appetite. These cells, which are located in the dorsal raphe nucleus (DRN), could become targets for drugs that control hunger signals to treat obesity.

These findings are the latest to suggest that eating and hunger are mediated by numerous biological processes in the brain. The authors discovered information that may also fill a gap in previous research by addressing obesity at a neuronal level.

It was previously discovered that the hormone leptin acts on neurons in the brain to suppress hunger. The authors report that injections of the hormone promote dramatic weight loss in patients with a deficiency, but many obese patients do not respond to therapy.

"Obesity is generally associated with leptin resistance," said researcher Jeffrey Friedman, MD, PhD. "And our recent data suggest that modulation of the activity of specific neurons with drugs could bypass leptin resistance and provide a new means for reducing body weight."

The authors discovered the subtypes of brain cells when whole-brain imaging revealed that DRN becomes activated in hungry mice. Further imaging of mice that were fed more than their normal amount of food revealed different activity, suggesting that the neurons were involved with feeding behavior, according to the study.

Next, the authors conducted a genetic analysis to determine which neurons in the DRN were involved with hunger. They found that neurons triggered by a full stomach released glutamate, while neurons triggered by hunger released the GABA neurotransmitter.

"There are 2 possibilities when you see something like that," said Alexander Nectow, PhD. "One is that the cells are just along for the ride -- they are getting activated by hunger but they're not actually driving the food intake process. The other possibility is that they are in fact part of the sense and respond mechanism to hunger -- and in this case, we suspected the latter."

After activating the glutamine-releasing neurons, the mice’s food intake was lessened and the animals lost weight, according to the study. The authors believe this finding confirms that the subset of DRN neurons drove food intake.

They also found that activating the GABA-releasing neurons in DRN increased food intake. By turning on these neurons, the authors reported that it also automatically turned off the satiety neurons, according to the study.

"We were excited to see that prolonged inhibition of these neurons could dramatically reduce body weight," said co-first study author Marc Schneeberger Pane.

These results may lead to new research exploring how the brain controls eating. The authors suggest that drugs targeting DRN neurons could be effective in treating patients with obesity.