OUR SCREAMING NEURONS AND WHY IT IS HARD TO DIET VOL. 1 NO. 33


agrpHaving trouble dieting? It may be due to negative feelings correlated with hunger making it hard to diet and lose weight. Hunger sensitive neurons in the brain may explain that problem.

Researchers, at the Howard Hughes Medical institute’s Janelia Research Campus, point to AGRP neurons as responsible for the negative feelings of hunger that make eating inevitable.

hunger_hormone-227x300The negative feelings correlated with hunger make it hard to diet and lose weight; these neurons lead to an explanation of that struggle, states Scott Sternson, a group leader at Janelia. In most settings where food is in abundance, AGRP’s message may seem counterproductive to dieting, but from an evolutionary point of view, it makes sense. For our ancestors, searching for food or water could mean moving into a hostile environment, which would require some internal override mechanism. “We suspect that what these neurons are doing is imposing a cost on not dealing with your physiological needs.”

AGRP neurons teach humans and animals to respond to sensory cues in indicating the presence of food. “We mouse eatingsuspect that these neurons are a very old motivational system to force an animal to satisfy its physiological needs. Part of the motivation for seeking food is to shut these neurons off,” says Sternson. Sternson and colleagues also showed that a different set of neurons specialized in unpleasant feelings of  thirst. These findings were reported in the journal Nature.

hunger“There was an early prediction that there would be neurons that make you feel bad when you were hungry or thirsty. This made sense from an intuitive point of view, but all of the neurons that had been looked at seemed to have the opposite effect,” he says. In previous studies, scientists discovered that neurons that encouraged eating did so by increasing positive feelings correlated with food.

“Some scientists had begun to suspect their ideas about a negative signal in the brain motivating hunger might be wrong. But their knowledge of the system was incomplete. AGRP neurons, located in a regulatory area of the brain known as the hypothalamus, were clearly involved in feeding behaviors: When the body lacks energy, AGRP neurons become active, and when AGRP neurons are active, animals eat. But no one had yet investigated those cells’ strategy for generating that motivation.”

Researcher Nicholas Betley and all conducted a series of behavioral experiments. They offered sated mice two flavored gels without any nutrient value. The mice sampled both flavors. The scientist turned on the AGRP neurons while they ate one of the two flavors. In the following tests, the mice avoided the flavor associated with the false hunger signal.

diagram of mouse brain
Click to enlarge image

Next, researcher Shengjin Xu used a tiny microscope to look inside the brains of the hungry mice and monitor the activities of AGRP neurons. “What came as a surprise,” Sternson says, “is that the AGRP neurons deactivated at the site of food—or even a signal that predicted food.”

“That wouldn’t make sense if the job of AGRP neurons was to make food taste better or if they directly controlled the individual actions that go into eating, which were two possibilities, Sternson says. But to encourage eating, a negative signal would need to turn off when an animal consumed food. So their imaging experiments further supported what they had learned in their previous experiments.”

So the next time you are trying to diet and you begin to feel those hunger pangs think about all those little AGRP cells that are crying out to be sated. That may be why it is so hard to diet when you are home next to the refrigerator or watching TV with all those food ads running one after the other. You can blame the AGRP cells for driving you to the brink of binge eating.

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