If you’ve ever fallen ill and found yourself barely able to stomach a spoonful of chicken soup, you already know that getting sick can be a major appetite killer.
Scientists studying the dissolution of hunger in response to illness have known for years that this process depends, in part, on the body’s concentration of a protein called interleukin 18 (IL-18). IL-18 is a cytokine — aka a chemical messenger of the body’s immune system — and, when elevated during periods of illness, infection and virus fighting, or injury, appears to suppress appetite.
Another key player implicated in the loss of hunger during or following bouts of being unwell is the Bed Nucleus of the Stria Terminalis (BST), a neural structure that communicates with the Lateral Hypothalamus (LH) to stimulate (or staunch) the desire to eat. (For clarity, a stimulated LH results in an increased appetite.)
Until recently, researchers didn’t know quite how the above chemical messengers and brain structures coordinated to eliminate appetite. They just knew all the above were, in some way, involved. To get to the root of the process, a team of scientists from The Scripps Research Institute compared how much lab mice ate after their BSTs were injected with IL-18. They then anesthetized the mice and removed their brains to peer under a microscope at the shape and connectivity of these regions of interest as well as the neuronal activity occurring therein.
In a paper published in this month’s edition of The Journal of Neuroscience, the researchers explain that under normal circumstances (i.e., without outside intervention from researchers injecting their BSTs with IL-18), neurons connecting each mouse’s BST to its LH are activated by glutamate, an “excitatory” neurotransmitter. This galvanizes mice to seek out food and eat to satiety. As their fullness increases, the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) builds up enough to inhibit activity in the LH, causing the mice to lose interest in eating further and walk away from the feeding bowls satisfied.
When IL-18 comes into play, however, this otherwise normal communication system is disrupted. IL-18 binds to receptors on key areas at the base of the BST-LH neuronal pathway, interfering in the release of glutamate and GABA and causing the mice to lose their appetites as their LH lacks adequate signaling input to spur hunger.
Mice whose BSTs were injected with IL-18 consumed remarkably less chow than mice who were spared the injections. And the brain slices of these IL-18 treated mice revealed significant differences in signaling between BST and LH neurons implicated in hunger and fullness when compared to the brain slices of mice operating under the influence of non-engineered biochemical cues.
“[O]ur data show that IL-18 acts on the adBST to reduce food intake, and this behavioral effect may result from reduced excitatory drive of Type III GABAergic neurons in the jcBST,” the researchers write in their paper. “This model is consistent with recent findings that activation of GABAergic BST neurons projecting to glutamatergic LH neurons dramatically increases food intake and provides new insights into how a proinflammatory cytokine may contribute to a key component of “sickness syndrome” (loss of appetite) via receptor-specific modulation of central neuronal circuitry that modulates feeding.”
Silencing the parts of our brains that make us hungry may strike some as an appealing solution to weight loss woes. But a lack of appetite can lead to a range of unfortunate health outcomes, especially for people with serious illnesses like cancer or AIDS. (Appetite loss in the extreme is called cachexia, morbidly known as “the last illness” for people with terminal illnesses, as it tends to accelerate patients’ declines.)
The researchers involved in the above study hope to apply their findings to developing treatments for chronic absences of hunger that accompany more debilitating illnesses. "Treating loss of appetite won't cure an underlying disease, but it could help a patient cope," Professor Bruno Conti, Ph.D., the study's senior author, said in a press release. "Many times, loss of appetite can compromise clinical outcome."
They also raised the possibility of using their insights to inform interventions aimed at curbing excessive hunger in obesity and other metabolic disorders.
Further studies are needed to see how these mouse model results map onto the brain regions of humans — and whether or not altering levels of cytokines in our species can help manage chronic appetite loss or insatiability. So stay tuned. And don't forgo your next flu shot as an attempt to nix lingering cravings for cupcakes just yet.