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Mouse Study Links Cooking Oil Fat to Psoriasis-Like Itch
In A Nutshell
- A breakdown product of linoleic acid, a fat found in cooking oils and packaged foods, triggered itching in mice by switching on a nerve receptor called Gpr35.
- Mice lacking the receptor in a group of nerve cells, or given a drug that blocks it, scratched less after EKODE exposure and in a psoriasis-like skin model.
- Human nerve tissue also carries the receptor, but whether the same process happens in people is untested.
- Itch dropped even though inflammation signals rose, so itch and inflammation may run on separate tracks.
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.
EKODE’s route to itch now has a named receptor. Whether lowering dietary linoleic acid or blocking Gpr35 relieves itch in people remains untested, so the cooking oil link is a lead for researchers, not yet advice for the kitchen.
Disclaimer: This article summarizes a peer-reviewed study for general readers and is not medical advice. The research was conducted mostly in mice and laboratory cells, and the findings may not apply to people. Consult a health care professional before changing diet or treatment for itch or any skin condition.
Paper Notes
Limitations
Several questions remain open, the authors note. They do not yet know exactly which skin cells produce the elevated EKODE seen in their psoriasis-like mouse model, though they suspect keratinocytes or immune cells moving into the area. An apparent mismatch also appeared between lab dish and live animal results for the Trpv1 channel: it was not needed for the initial chemical response in isolated cells, but removing it in living mice still reduced itching. The authors suggest it may boost the signal instead of detecting EKODE directly. Dietary changes, such as lowering linoleic acid intake, were not tested, and the authors call diet studies in human populations challenging, with animal studies as the next step. They also have not yet determined which versions of the human Gpr35 gene are active in human sensory nerve tissue or how those versions respond to EKODE. Beyond the authors’ own list, the experiments relied mostly on mice and cultured cells, test groups were small, and the human tissue staining came from two samples, so the human findings show the receptor is present, not that it causes itch in people. Psoriasis was modeled with a skin cream that causes psoriasis-like inflammation in mice, which does not fully replicate the human disease.
Funding and Disclosures
Startup funds from North Carolina State University to corresponding author Santosh K. Mishra funded the work, alongside support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and private gift support. One author was supported by an institutional training grant, and two authors, Christopher E. Ramsden and Gregory S. Keyes, were supported by the Intramural Program of the National Institute on Aging. Mishra filed an invention disclosure at North Carolina State University titled “Therapeutic Potential of GPR35 Blockers in inflammation and itch,” with Brian S. Kim as co-inventor; the paper states that an IP filing is not applicable. Kim is a co-founder of Alys Pharmaceuticals and Neurommune Therapeutics, has consulted for numerous pharmaceutical and biotechnology companies, holds stock in several, and holds a patent for the use of JAK1 inhibitors for chronic itch. The remaining authors declared no competing interests.
Publication Details
Titled “Metabolic sensor Gpr35 links dietary lipids to itch mediating neural circuits,” the study was published online October 29, 2026, in Communications Biology (volume 9, article 1393). The paper was received February 10, 2026, and accepted September 21, 2026. The first author is Joshua J. Wheeler, and the corresponding author is Santosh K. Mishra of North Carolina State University College of Veterinary Medicine. Additional authors include Alla Lyfenko, Nesia A. Zurek, Keaton Song, Andy Wangzhou, Sruti Bontala, Ojasvi Deep, Jacob Casey, Ramsey Kubofcik, Daniel L. Schaffer, Hassan Melhem, Gregory S. Keyes, John M. Davis, Jan Hendrik Niess, Theodore J. Price, Christopher E. Ramsden, Brian S. Kim, and Sascha R. A. Alles, representing institutions including NC State University, Cincinnati Children’s Hospital Medical Center, Icahn School of Medicine at Mount Sinai, University of Texas at Dallas, University of Basel, University of Illinois at Chicago, Northwell Health, and the National Institutes of Health. The paper’s DOI is https://doi.org/10.1038/s42003-026-11087-x. The article is open access under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 license.
