Using experimental techniques like calcium imaging in freely moving mice, optogenetics, and chemogenetics, a study in the journal Cell Metabolism this week demonstrated, faced with a decision between sex and food, moderately hungry mice will opt to interact with the opposite sex instead of attending to their nutritional needs when their brains are stimulated by leptin.

The findings published on February 23, in the article “Complementary lateral hypothalamic populations resist hunger pressure to balance nutritional and social needs,” could help develop better therapeutic strategies for diseases like obesity and eating disorders.

Tatiana Korotkova, PhD, professor of physiology at the University of Cologne is the senior author of the study.

“We can only pursue one behavior at a time, so our brain has to somehow compute what will be the most rewarding behavior, or what is our most urgent need,” said Tatiana Korotkova, PhD, professor of physiology at the University of Cologne and senior author of the study.

“We usually think about neurons having a particular function, but we found that one cell can actually encode multiple different stimuli. This makes sense biologically because behaviors need to be coordinated, and it’s much more efficient to coordinate behaviors with the same cell than by many different cell types somehow communicating with each other,” Korotkova added.

To understand how the brain ranks innate behaviors like eating, drinking, socializing, and mating, Korotkova’s team studied neurons in the mouse lateral hypothalamus, a region of the brain involved in feeding that express receptors for leptin and neurotensin, hormones that mediate messages of hunger and thirst. The researchers were surprised to find, these neurons also guide social behavior and help balance nutritional and social needs.

“We were astonished to find that the lateral hypothalamus links feeding and drinking to social behaviors,” said Anne Petzold, PhD, a postdoctoral neuroscientist at the University of Cologne and the lead author of the study. “Activating leptin receptor neurons makes mice prioritize social interaction despite acute hunger or thirst. This makes sense biologically because mating partners are not something that you have around all the time, and so one must be able to ignore hunger or thirst to be able to engage in mating.”

The researchers compared behaviors among well-fed mice with unlimited access to food, acutely hungry mice with no access to food overnight, and chronically hungry mice with restricted access to food over five days.

“It was a huge advantage that we could record the activity of neurons in a freely behaving animal,” said Korotkova. “We could really see how neuronal activity changes during particular behaviors, and we could track and change the activity of individual cells with a high time precision.”

The researchers found, when mice ate, the neurons expressing leptin receptors in the lateral hypothalamus were inhibited whereas when mice interacted with members of the opposite sex, these neurons were activated. When the investigators selectively stimulated these leptin receptor bearing neurons using light and chemical signals, it had little effect on the behavior of satiated mice, who generally prioritized socializing over eating, but it induced acutely hungry mice to switch their priorities. Upon leptin stimulation, acutely hungry mice were slower to approach food, ate less, and spent more time socializing with potential mates.

Hormones leptin and neurotensin help mice balance their nutritional and social needs [Petzold et al., Cell Metabolism, 2023].
However, leptin stimulation was not capable of overriding hunger in chronically hungry mice. These mice showed no reduction in appetite even upon leptin activation. On the other hand, Korotkova’s team found, activating neurotensin neurons in mice using light and chemical signals, increased drinking at the expense of socializing with both sexes.

“So, we have this system which can only regulate moderate hunger, but not strong hunger,” said Korotkova. “This circuit might contribute to why diets don’t work: it’s not a problem to reduce your food intake for a short time, but it doesn’t work if you try to do it for longer.”

In future studies, Korotkova and her team intend to understand the change in activities of neurons expressing leptin and neurotensin receptors during the progression of obesity and eating disorders.

Previous articleNext-Gen BLI Technology Accelerating Antibody Discovery
Next articleRNA Kept “In Check” by Shape-Shifting Enzyme