Imagine that a temporary supercomputer lives inside your head… but it sometimes crashes when you see a chocolate bar in the distance. This supercomputer is your brain , and its main firmware is installed in the hypothalamus , a small central hub that regulates everything: hunger, satiety, rhythm, sleep, stress… and, yes, even how appetizing a croissant is at three in the morning. It's all there. And the signals that arrive come from various sources—what you ate, how you slept, whether you were anxious, whether you have genes that facilitate fat accumulation—and are integrated to calculate whether we should eat or store energy.
But who really controls the controller? This is where neurobiology takes a turn.
1. Neural circuits and biochemical sensors
In the hypothalamus, there are circuits such as the central melanocortin system , which combines neurons that produce NPY (which increases appetite) with others that produce POMC—modulating both how much we eat and energy metabolism. When these pathways malfunction, for example due to a mutation in the melanocortin-4 receptor, severe obesity can result.
2. Hormones that act as “flight messengers”
The gut and other organs produce hormones like GLP-1 and PYY , which are released after we eat and tell the brain that we are full.
- GLP-1 , secreted by intestinal cells and also by some regions of the brain, increases the feeling of fullness, delays gastric emptying, and facilitates insulin production. GLP-1 agonists (such as semaglutide, tirzepatide, etc.) mimic this effect, leading to significant weight loss and reduced appetite.
- PYY , released into the intestine after a meal, reduces appetite mainly by slowing down the stomach, helping to prolong the feeling of satiety.
3. Brain Maps: The GPS of Hunger
Recently, researchers created a detailed map of the cells in the human hypothalamus, revealing thousands of cell types and how they interact. This atlas, produced using technologies such as single-cell RNA sequencing and spatial transcriptomics, could guide the development of more personalized and effective medications with fewer side effects.
4. Challenges in Pharmacology: From Blood to Brain
There are still bugs in the system: many GLP-1 agonists have difficulty crossing the blood-brain barrier and directly activating brain receptors. In animal models, stimulating the brain's own GLP-1 neurons has shown stronger effects on reducing eating, but the effect is temporary. The big challenge is to create drugs that reach the right targets, for a long time, and with fewer side effects, such as nausea.
5. And in everyday life? There are natural tricks!
A diet rich in fiber (vegetables, whole grains), healthy fats (such as olive oil or omega-3 fatty acids), and lean protein naturally stimulates GLP-1 production in the gut. Regular exercise can also increase and prolong GLP-1 levels, helping to control appetite and improve metabolism.
In short:
Hunger is controlled by the brain, especially the hypothalamus, which integrates hormonal, genetic, environmental, and emotional signals to regulate appetite. Science can already manipulate part of this system with drugs like GLP-1 agonists, but lifestyle habits remain powerful tools for influencing this internal "control panel."
Reference:
Johansen, VBI, et al. (2025). Brain control of energy homeostasis: Implications for anti-obesity pharmacotherapy. Cell , 188. https://doi.org/10.1016/j.cell.2025.06.010