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Credit: Sam Eichenwald

The unpleasant feeling of hunger can be difficult to ignore, and Penn researchers have sought to explain the biological mechanism behind these impulses in a new study published in the journal Cell Reports.

Using brain scans of mice, biologists at Penn found that AgRP neurons, which indicate hunger and spark the impulse to eat, are lowered when the body sees or smells food, as well as when it actually consumes it. Because of the association between the food and the decrease in the sensation of hunger, even seeing or smelling the food can indicate to the brain that the body is receiving the nutrients it needs. 

According to new research by Penn assistant professor of biology J. Nicholas Betley and his colleagues, this decline in activity in AgRP neurons only lasts 200 seconds if the body does not consume the calories it anticipates. If the body does, in fact, consume the calories, the drop in AgRP neurons remains low. 

“When these neurons are firing, they’re basically telling you, ‘You’d better go get food; you’re starving,'" Bentley said, Penn News reported. “They’re a sensitive alarm system. And what this study conclusively demonstrated is that nutrients are the primary regulators of this alarm system.”

The “anticipatory drop” in AgRP neurons, prompted by the sight and smell of food, was largely dependent on whether or not the mice in the study associated the food with calorie consumption. With a larger drop in AgRP levels when the mice anticipated they would consume calories.  

The only situation where the researchers were able to observe sustained reduction in AgRP neuron activity was when the mice actually consumed calorie-containing food. During an experiment that measured the difference in levels of the AgRP neurons in mice when they consumed calorie-free gel and when they consumed calorie-filled gel, the levels only stayed low when the mice consumed calorie-filled gel. The "anticipatory drop" in AgRP neurons was less significant as the mice became familiar with the gel and knew not to anticipate the suppression of hunger. 

The team then identified three hormones — cholecystokinin, peptide tyrosine tyrosine, and amylin — normally emitted during digestion as significant contributors to turning off neuron activity. Bentley pointed out that a combination of the three “may have relevance to treating obesity in humans,” Penn News reported.

Further investigating this technique, specifically discovering ways to trigger the release of these hormones, researchers hope to develop “behavioral strategies that could reduce total food intake” centered around minimizing AgRP neuron activity. 

“It would be interesting to see whether consuming smaller meals more frequently might lead to less activity in the neurons and thus less food intake overall,” Betley told Penn News. “Or maybe we can develop better combinations of foods or better ways of eating so we can avoid that 9 p.m. binge on Oreo cookies when you’ve had a really great diet all day.”