Feeling hungry doesn’t just make you reach for a snack – it may also change your immune system.
In a recent study in mice, we found that simply perceiving hunger can change the number of immune cells in the blood, even when the animals hadn’t actually fasted. This shows that even the brain’s interpretation of hunger can shape how the immune system adapts.
Our new research published in Science Immunology challenges the long-standing idea that immunity is shaped primarily by real, physical changes in nutrition, such as changes in blood sugar or nutrient levels. Instead, it shows that perception alone (what the brain “thinks” is happening) can reshape immunity.
We focused on two types of highly specialised brain cells (AgRP neurons and POMC neurons) that sense the body’s energy status and generate the feelings of hunger and fullness in response. AgRP neurons promote hunger when energy is low, while POMC neurons signal fullness after eating.
Using genetic tools, we artificially activated the hunger neurons in mice that had already eaten plenty of food. Activating this small but powerful group of brain cells triggered an intense urge to seek food in the mice. This finding builds on what multiple previous studies have shown.
To our surprise, though, this synthetic hunger state also led to a marked drop in specific immune cells in the blood, called monocytes. These cells are part of the immune system’s first line of defence and play a critical role in regulating inflammation.
Conversely, when we activated the fullness neurons in fasted mice, the monocyte levels returned close to normal, even though the mice hadn’t eaten.
These experiments showed us the brain’s perception of being hungry or fed was on its own enough to influence immune cell numbers in the blood.
To understand how this axis between the brain and the immune system works, we then looked at how the brain communicates with the liver. This organ is important in sensing energy levels in the body. Research has also shown the liver communicates with bone marrow – the soft tissue inside bones where blood and immune cells are made.
We found a direct link between the hunger neurons and the liver via the sympathetic nervous system, which plays a broad role in regulating functions like heart rate, blood flow, and how organs respond to stress and energy demands. When the hunger neurons were turned on, they dialled down nutrient-sensing in the liver by reducing sympathetic activity.
This suggests that the brain can influence how the liver interprets the body’s energy status; essentially convincing it that energy is low, even when actual nutrient levels are normal. This, in turn, led to a drop in a chemical called CCL2, which usually helps draw monocytes into the blood. Less CCL2 meant fewer monocytes circulating.
We also saw that hunger signals caused the release of a stress hormone called corticosterone (similar to cortisol in humans). This hormone on its own didn’t have a big effect on immune cell numbers, at least not at the levels that would typically be released while fasting.
Much higher levels of stress hormones are usually needed to affect the immune system directly. But in this case, the modest rise in corticosterone worked more like an amplifier. While it wasn’t enough to trigger immune changes by itself, it was crucial for allowing the response to happen when cooperating with signals coming from the brain.
This further illustrate how the body’s stress system and immune changes are scalable and how they adjust depending on the nature and intensity of the stressful event.
Why might this happen?
Why would the brain do this? Although we haven’t formally tested this, we think one possibility is that this complex, multi-organ communication system evolved to help the body anticipate and respond to potential shortages. By fine-tuning energy use and immune readiness based on perceived needs, the brain would be able to coordinate an efficient whole-body response before a real crisis begins.
If the brain senses that food might be limited (for example, by interpreting environmental cues previously associated with food scarcity) it may act early to conserve energy and adjust immune function in advance.
If these findings are confirmed in humans, this new data could, in future, have real-world implications for diseases where the immune system becomes overactive – such as cardiovascular diseases, multiple sclerosis, and wasting syndrome in cancer patients.
This is of further relevance for metabolic and eating disorders, such as obesity or anorexia. Not only are these disorders often accompanied by chronic inflammation or immune-related complications, they can also alter how hunger and fullness are computed in the brain.
And, if the brain is able to help dial the immune system up or down, it may be possible to develop new brain-targeted approaches to aid current immuno-modulatory therapies.
Still, there’s much we don’t know. We need more studies investigating how this mechanism works in humans. These studies could prove challenging, as it isn’t possible yet to selectively activate specific neurons in the human brain with the same precision we can in experimental models.
Interestingly, more than a century ago a Soviet psychiatrist, A. Tapilsky, conducted an unusual experiment where he used hypnosis to suggest feelings of hunger or fullness to patients. Remarkably, immune cell counts increased when patients were told they were full and decreased when they were told they were hungry.
These early observations hinted at a powerful connection between the mind and body, well ahead of today’s scientific understanding and are eerily prescient of our current ability to use powerful genetic tools to artificially generate internal sensations like hunger or fullness in animal models.
What’s clear is that the brain’s view of the body’s energy needs can shape the immune system – sometimes even before the body itself has caught up. This raises new questions about how conditions such as stress, eating disorders and even learned associations with food scarcity might drive inflammation and disease.
Giuseppe D’Agostino, Senior Lecturer, Division of Diabetes, Endocrinology & Gastroenterology, University of Manchester and João Paulo Albuquerque, Postdoctoral Researcher, Physiology and Metabolism, University of Manchester
This article is republished from The Conversation under a Creative Commons license. Read the original article.
