A dietary-fat derivative activates an itch pathway in mice
A molecule derived from linoleic acid activated a sensory-neuron receptor involved in itch, linking lipid metabolism with skin inflammation in experiments. Removing or blocking parts of the pathway reduced symptoms in mouse disease models. The peer-reviewed study also examined human sensory cells, but establishes neither a patient treatment nor dietary advice.
Science··Morning
A lipid signal reaches sensory nerves
A breakdown product of dietary fat activated a receptor on sensory neurons in experiments examining chronic itch. Published on October 29 in Communications Biology, the peer-reviewed research connected the molecule EKODE with GPR35, a cellular receptor involved in transmitting itch signals. The team tested cells and mouse models of inflammatory skin disease. EKODE forms through oxidation of linoleic acid, a fatty acid found in nuts, seeds and vegetable oils that also contributes to normal skin function. Previous work detected high concentrations of the derivative in psoriatic lesions and observed scratching after exposure in mice. The new experiments pursued the molecular connection with sensory signaling.[1], [2]
Blocking the pathway reduced scratching in mice
The researchers examined mouse sensory neurons and cultured human neurons from dorsal-root ganglia, the sensory nerve clusters near the spinal cord. They confirmed GPR35’s presence in neurons carrying channels associated with pain, temperature and itch. Receptor activation engaged BNP, a small protein involved in itch signaling, connecting the skin with the spinal cord. In a psoriasis model, mice without GPR35 had less scratching and inflammation than animals retaining the receptor. Removing BNP also reduced those responses. A receptor blocker reduced scratching in an eczema model, extending the observations to another skin condition. These interventions support the pathway’s involvement in the tested animals.[1], [2]
A potential target needs human validation
Santosh Mishra, a professor at North Carolina State University’s College of Veterinary Medicine, was corresponding author; postdoctoral researcher Joshua Wheeler was first author. The researchers identify GPR35 as a possible therapeutic target for chronic skin conditions. Human sensory-cell findings establish the presence of relevant machinery, but clinical benefit and safety need further investigation. How inflamed skin produces EKODE, including its cellular origin and the circumstances of production, also remains incompletely resolved. The work did not test whether removing a particular oil from people’s diets treats itch or psoriasis. Its findings concern a lipid-sensitive neural pathway rather than an established dietary or medical treatment. The US National Institutes of Health supplied approximately half the support for the work, which included researchers in the United States and Switzerland.[1], [2]
