Yale researchers have helped uncover the cellular mechanism that explains how changes in our diet may have led to increasing rates of autoimmune diseases like multiple sclerosis.

Using genetically modified mice, the researchers showed that altering hypothalamic neurons to simulate satiety increased inflammation of body tissue. The finding helps explain how immune system-triggered inflammation often occurs after eating and carries implications for developing new treatments for autoimmune disorders, said senior author and comparative medicine professor Tamas Horvath of the Yale School of Medicine. The paper was published online on March 25 in the journal Proceedings of the National Academy of Sciences.

“This is a fantastic paper because it shows really for the first time a real mechanistic connection between hunger-promoting neurons and peripheral adaptive immunity,” said Louisiana State immunobiology professor Vishwa Dixit, who was not involved in the study.

The researchers explored the link between appetite and immune response through AgRP neurons, which are found in the hypothalamus and promote appetite. When Horvath and the team simulated a state of satiety by chronically suppressing the neurons, they observed an increased immune response indicated by increased T cell activation. Horvath called the mechanism a “double-edged sword,” as acute inflammation is a key defense against various pathogens, but chronic inflammation can lead to autoimmune diseases.

The increased availability of energy-rich foods nationwide has correlated with growing prevalence of autoimmune diseases, Dixit said.

“What that is doing is tipping the balance of the base of inflammation towards more of a pro-inflammatory state,” he said. “That is thought to be responsible in part for several chronic diseases that stem from inflammation, ranging from Alzheimer’s diseases to diabetes.”

Horvath said he hopes to conduct studies in humans and non-human primates to show whether promoting hunger can suppress autoimmune diseases. By controlling food intake and the level of hunger subjects reach during the daily cycle, he said he should be able to modulate immune inflammatory responses.

But treatment in humans is still a distant prospect, said Yale neurology professor David Hafler, who was not affiliated with the study. The paper did not explore a mechanism that connects the knockout of the AgRP neuron to the increased immune response, which will be a key step in developing treatments for autoimmune diseases that exploit the pathway that Horvath explored. Furthermore, studies using model organisms like mice always require more inquiry before the mechanisms can be translated to human clinical applications, he said.

Hafler said this paper adds to a growing literature that implicates the whole metabolic system in the functioning of the immune system. In March, Hafler was the senior author of a paper published in the journal Nature showing that table salt can exacerbate symptoms of autoimmune diseases.

According to the National Institutes of Health, five to eight percent of Americans suffer from autoimmune diseases.