If you struggle with losing weight, you are already familiar with two facts of life: eating food tastes great and being hungry feels uncomfortable. Researchers at the Howard Hughes Medical Institute decided to examine half that equation and soon discovered the biology underlying hunger is not so simple after all. Based on their results, they believe specific brain cells in the hypothalamus make you unhappy in an effort to motivate you to eat.

In other words, your brain cells will teach you a negative lesson if you don't reach for that slice of pie.

How hunger works

When food is restricted and an overall energy deficit results, past animal research has demonstrated agouti-related protein-expressing neurons (AGRP) located in the hypothalamus begin to fire. This activity leads to food-seeking behavior in the animals and, ultimately, they start eating. Generally, the hypothalamus is responsible for the production of many essential hormones governing our physiologic functions, including our body temperature, thirst, hunger, sleep, mood, and sex drive.

For the current study, the researchers wanted to know whether these AGRP neurons linked to a bodily energy deficit transmitted positive or negative signals. In other words, do these signals contribute to the negative feeling of hunger pangs?

They designed a series of experiments using mice. Before the tests began, the mice were fitted out with either photoactivatable AGRP neurons or virally-transduced AGRP neurons able to be inhibited with a drug. The researchers planned to either stimulate or inhibit the neurons in the mice in order to see how they responded when faced with food.

Let the experiments begin!

During a series of flavor preference tests, the researchers stimulated AGRP neurons in some mice and then compared their behavior to unstimulated mice; then, they inhibited AGRP neurons in some mice but not others and compared their behavior. In one experiment, the stimulated mice showed a weakened desire for a previously preferred flavored gel compared to unstimulated mice. According to the researchers, this suggests a once tasty flavor became a less pleasant experience whenever AGRP neurons became active. By contrast, the food-restricted mice showed an increased preference for their favorite gel whenever AGRP neurons were inhibited. This also suggests the AGRP neurons aroused negative feelings.

During a series of place preference experiments, the mice were offered two chambers to explore while the researchers observed their behavior. Well-fed mice avoided chambers in which they had received AGRP stimulation, apparently an undesirable feeling. Similarly, hungry food- restricted mice spent more time in chambers where they had previously received AGRP inhibition. They, too, preferred relief and not stimulated AGRP.

The researchers ran a complementary series of experiments activating thirst-promoting neurons and found similar results.

Together, these results suggest AGRP neurons stimulate negative signals, the researchers say. Like a Pavlovian response conditioned through negative experiences, AGRP neurons teach us to eat through the negative experience of hunger. This is the direct opposite of other hunger-related neurons, which stimulate reward pathways and result in positive feelings when we satisfy hunger.

Apparently, our food related behaviors are fine-tuned by both kinds of neurons. Though this biological system is complex, the authors believe their work could lead to innovative strategies for helping people to diet.

Source: Betley JN, Xu S, Cao ZFH, et al. Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature. 2016.

Published by Medicaldaily.com