Oxidation of the Unsaturated Fatty Acid Linoleic Acid Generates Highly Potent TRPA1 Agonists

Polyunsaturated fatty acids (PUFAs) play important roles in health and biological functions. However, their high susceptibility to oxidation leads to the formation of unpleasant astringent sensations, posing a significant challenge in food production. In this study, to elucidate the molecular mechanisms underlying astringency induced by oxidized PUFAs, linoleic acid (LA), a representative PUFA, was used as a model. The effects of its oxidation products on two key human astringency-related receptors, transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1), were analyzed. Ten oxidation products were identified from oxidized LA, among which 9-HpODE and 13-HpODE exhibited 5- to 10-fold higher TRPA1 activity than LA. This study is the first to demonstrate that PUFA oxidation generates highly potent TRPA1 agonists. Our findings propose a novel mechanism for astringency induced by oxidized PUFAs, wherein PUFA oxidation products activate TRPA1. PRACTICAL APPLICATIONS: This study is the first to demonstrate that oxidation of linoleic acid, a model polyunsaturated fatty acid (PUFA), produces potent agonists of the pungency receptor TRPA1. Part of the molecular mechanism underlying pungent sensation induced by oxidized PUFAs was elucidated. These findings may contribute to the development of novel strategies for controlling the pungency of oxidized PUFAs by combining TRPA1 response suppression with conventional approaches such as oxidation inhibition.