Mouse Study Links Cooking Oil Fat to Psoriasis-Like Itch
Few things are more maddening than an itch that refuses to quit. New research in mice points to a surprising culprit: a breakdown product of linoleic acid, a fat found in cooking oils and packaged foods. The compound, called EKODE, latches onto a nerve receptor called Gpr35 and sets off itching. It also turns up at much higher levels in psoriasis-affected skin than in unaffected skin from the same patients, according to earlier work.
Gpr35 works like a lock, and EKODE fits it like a key. Once the two connect, a relay of nerve signals leads to scratching. The work, published in the journal Communications Biology, gives scientists a look at how a fat from the diet could end up triggering itching and skin inflammation.
Linoleic acid is the most abundant omega-6 fat in both skin and modern diets. Earlier animal studies found that diets high in it raise inflammation-promoting compounds in skin and heighten pain sensitivity, and people with obesity who eat modern industrialized diets are more likely to develop psoriasis, a long-lasting skin condition marked by itchy, inflamed patches.
A Fat Breakdown Product Switches On Nerve Cells Tied to Chronic Itch
Scientists already knew that injecting EKODE under a mouse’s skin triggers scratching. What remained unknown was which receptor on nerve cells detects it.
To find out, the team exposed nerve cells from mouse tissue near the spinal cord to EKODE and watched for a burst of calcium, a sign that a cell has switched on. About 9% of the cells responded, and those cells also reacted to histamine, a classic itch chemical, and to other known itch and pain triggers. Chemical blockers showed that the response depended on a large family of receptors on the cell surface.
From there, researchers zeroed in on Gpr35. They placed the receptor into lab-grown human kidney cells along with a partner protein that helps nerve cells sense itch and pain. Only cells carrying both pieces responded to EKODE with a calcium signal. Neither piece alone was enough. Nerve cells from mice engineered to lack Gpr35 also responded less.
Blocking the Receptor Calms Chronic Itch in Mice
To test the receptor in living animals, researchers bred mice that lacked Gpr35 in a large group of pain- and itch-sensing nerve cells. Test groups were small, often 6 to 8 mice each. After an EKODE injection, these mice scratched less than normal mice did. Both groups scratched normally after a histamine injection, so the receptor appears to matter for the EKODE route specifically, not for every kind of itch.
A drug that blocks Gpr35 produced a similar result. A single dose, given through the bloodstream, cut EKODE-driven scratching. The same drug also eased scratching in mouse models of psoriasis-like skin inflammation, induced with an irritating cream, and of atopic dermatitis, another itchy skin condition. In the psoriasis-like model, skin treated with the cream contained measurable EKODE, while skin given only a Vaseline control had none.
Gpr35 sits on nerve cells alongside a chemical messenger called Nppb, known to help carry itch signals to the spinal cord. Roughly half of the Gpr35 nerve cells in mice also carried Nppb, and mice lacking Nppb scratched less after EKODE and in the psoriasis-like model. The authors propose a relay: EKODE flips on Gpr35, which triggers release of the messenger, which carries the signal onward.
Mice without Gpr35 also took longer to pull away from very hot surfaces, including a plate heated to about 131 degrees Fahrenheit. The result hints that the receptor plays a part in intense heat pain. Reactions to moderate heat, pressure, and cold were unchanged.
Human Nerve Tissue Carries the Same Itch Receptor
Most of the experiments used mice, which raises an obvious question: does any of it apply to people? To check, the researchers analyzed existing genetic data from human sensory nerve tissue and found the Gpr35 gene active there, overlapping with cells that make the itch messenger. Staining of human nerve tissue from two samples showed that every cell making the messenger also carried Gpr35. Researchers have not yet tested whether EKODE activates the human version of the receptor.
An earlier large human genetic study, cited by the authors, linked variations in the Gpr35 gene to psoriasis risk. The authors suggest that differences in this receptor could make some people more prone to chronic itch and skin inflammation.
One result stood out in the psoriasis-like model. Mice lacking Gpr35 had thinner skin and scratched less, yet they had higher levels of two inflammation signals tied to psoriasis. Itch in these mice appears to run on a track separate from that inflammation pathway, which may help explain why some patients keep itching despite anti-inflammatory treatment. Targeting the nerve pathway directly could offer a fuller fix.
Source: https://studyfinds.com/cooking-oil-fuels-chronic-itch/
