Researchers seek to help people 'switch off' hunger in the brain

Researchers seek to help people 'switch off' hunger in the brain

PanARMENIAN.Net - Many think that controlling food cravings and sticking to a diet depend largely on willpower, but biology has a different story to tell. Now, new research shows that a complex interplay between calories, digestion hormones, and neurons determines what you eat and when, Medical news Today says.

Researchers at the University of Pennsylvania in Philadelphia — led by J. Nicholas Betley, an assistant professor in the Department of Biology in the university's School of Arts and Sciences — delve deeper into the interplay between the gut and the brain.

The researchers looked at what it is that triggers the appetite-stimulating neurons, and — more importantly for weight management efforts — what it is that switches them off.

The so-called agouti-related protein-expressing neurons (AgRP) are neurons in the hypothalamus that become activated when you are hungry. As Betley explains, "When these neurons are firing, they're basically telling you, 'You'd better go get food; you're starving.'"

AgRP neurons are "a sensitive alarm system," Betley says. But, apart from by eating, is there any other way that you can turn the alarm system off?

For the study, the team wanted to look more closely at the difference between how these neurons are shut down upon eating, and how they are shut down by the mere sight and smell of incoming food.

To do so, Betley and team used in vivo calcium imaging — a method that allows the researchers to track the activity of neurons with a high degree of specificity — to study genetically modified mice.

In separate trials, the mice were offered three different meals: regular chow (with which they were already familiar, so they knew how it tasted and smelled); a calorie-free, strawberry gel that was wholly unfamiliar to the rodents; and the same gel but this time with calories.

As expected, when seeing the standard chow, the mice associated its smell and appearance with satiety, so their AgRP neurons decreased in activity.

But when the rodents were given the calorie-free gel, seeing and smelling the food did not affect the neurons: their activity levels stayed just as high.

After eating the calorie-free gel, AgRP neuronal activity decreased, but only for a little while. The more repeatedly the mice were given the gel, the smaller was the decrease in the activity of the neurons, indicating that the rodents had come to associate the gel with a low amount of calories.

Finally, when the same mice received the calorie-containing gel, AgRP neurons decreased in activity and continued to "lay low" for a long time.

"[W]hat this study conclusively demonstrated," says Betley, "is that nutrients are the primary regulators of this alarm system," referring to AgRP neurons.

The findings prompted the researchers to figure out ways in which to "manually" control the activity of AgRP neurons.

So, they administered the rodents three hormones that are usually secreted during digestion: cholecystokinin, peptide tyrosine, and amylin.

Each of these hormones led to a significant decrease in the mice's AgRP neuronal activity, and the more of each hormone they received, the stronger was the diminishing effect on the mice's neuronal activity.

Betley notes that a similar cocktail may work for treating obesity in humans. He further comments on the relevance of the findings for humans.

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