A team from the University of Cologne has uncovered how the brain helps us eat even when anxiety tries to stop us. The discovery centers on leptin, a hormone that signals the brain when the body has enough energy.
Using high-resolution imaging in mice, researchers identified a network of leptin-sensing neurons in the lateral hypothalamus, a region that coordinates hunger and motivation. These neurons became active when animals overcame fear to explore or eat in stressful settings.
“We saw that these neurons get activated whenever animals overcame anxiety and freely explored exposed areas or approached food within them,” said Rebecca Figge-Schlensok, a doctoral researcher at the University of Cologne. “When we boosted this activity, mice explored more and were able to eat in challenging contexts.”
In more anxious mice, input from the prefrontal cortex, a region involved in cognitive control, suppressed the activity of these anxiety-relieving cells, preventing that behavioral flexibility.
“Increased input from the prefrontal cortex provided a mechanistic handle for why more anxious individuals fail to recruit this anxiety-reducing circuit,” said Dr. Anne Petzold, co-first author of the study.
The team also tested the circuit in a model of anorexia nervosa, where mice with limited food access often develop excessive exercise behaviors. Stimulating the leptin-sensitive neurons helped curb this overactivity, hinting that this pathway could be involved in both anxiety and eating disorders.
“Anxiety and anorexia nervosa often go hand in hand — and anorexia has the highest mortality rate of any psychiatric disorder,” said Professor Tatiana Korotkova, senior author and director of the university’s Institute for Systems Physiology. “By identifying a leptin-sensitive hypothalamic node that restrains anxiety-driven locomotion without suppressing normal activity, we begin to understand how emotional state and energy balance intersect in the brain.”
The findings, published in Nature Neuroscience, may eventually help scientists design treatments that rebalance emotional and metabolic control, revealing how closely the brain’s need for calm and its need for food are connected.
This work was supported by the European Research Council and the German Research Foundation through multiple research programs at the University of Cologne, including its Cluster of Excellence on Aging Research. Open-access funding was provided by the University of Cologne.