Why can’t some people stop eating? The hungry brain may be to blame

Dinner table with food and people eating
Manipulating neurons in the brain may be the key to helping people who don't feel full after they eat. shironosov/iStock/Getty Images Plus

Most people of normal weight don’t crave a cheeseburger right after they eat a full meal. But some people who struggle with obesity are still just as ravenous after they’ve chowed down as they were before. Now scientists at Beth Israel Deaconess Medical Center (BIDMC) believe they’ve discovered why the process of feeling too full to eat any more goes awry in some people—and the culprit, they say, lies deep in the brain.

The BIDMC team focused on the brain’s insular cortex, which has been shown in previous studies to be critical when people are deciding whether or not to pursue food. The insular cortex becomes more active when we are hungry, but then quiets down after a meal. Working in mice, the scientists discovered they could manipulate the exact neurons that govern this process—in essence turning on and off brain signals that govern eating behavior.

The scientists activated certain neurons in the hypothalamus that express the gene for Agouti-related protein (AgRP), which has been shown in past experiments to prompt feeding. When they stimulated those neurons after the mice had eaten and were full, the animals started eating again after seeing food. In fact, they acted as if they hadn’t seen food in a long time, said Bradford Lowell, M.D, Ph.D, professor of medicine at BIDMC and Harvard Medical School, in a press release.

"These AgRP neurons cause hunger—they are the quintessential hunger neuron," Lowell said. "It's a major advance to learn that we can artificially turn them on and cause full mice to work to get food,” he added.

It was far from an easy feat, though. The insular cortex is hard to reach in mice, so the BIDMC team used a mini periscope that allowed them to monitor neurons in that region of the brain while the mice were awake and responding to food. They employed genetic methods to turn on and off AgRP neurons. The results suggest that similar techniques might be used to dial down the neurons and thereby suppress the urge to eat in response to the mere presence of food.

The search for an effective weight loss drug continues at labs around the world, though many of the recent advances have focused on altering metabolism. Last month, scientists at the Salk Institute announced that when they gave mice an experimental compound that activates the gene PPAR delta, for example, it improved their ability to exercise and activated genes that help burn fat. Several research groups are looking for ways to convert unhealthy white fat into obesity-fighting brown fat, including scientists at the University of Pennsylvania, who have identified protein complexes that might provide pathways for doing just that.

Lowell and his team at BIDMC are taking advantage of their ability to see into the mouse brain’s insular cortex. They’re switching individual cells on and off to gain insight into how hunger cues in people—like seeing a picture of that cheeseburger—may influence eating. And they are working on unlocking the precise brain circuitry that influences how people weigh the pros and cons of eating particular foods.

"Huge questions remain,” Lowell said, “but they are now addressable thanks to these new imaging methods."