Specific Hydroxy Fatty Acids in Royal Jelly Activate TRPA1

This is the first report of TRPA1 activation by fatty acids. Activation of TRPA1 and TRPV1 induces thermogenesis and energy expenditure enhancement. In this study, we searched for novel agonists of TRPA1 and TRPV1 from a nonpungent food, royal jelly (RJ). We measured the activation of human TRPA1 and TRPV1 by RJ extracts and found that the hexane extract contains TRPA1 agonists. The main functional compounds in the hexane extract were trans-10-hydroxy-2-decenoic acid (HDEA) and 10-hydroxydecanoic acid (HDAA). These are characteristic fatty acids of RJ. Their EC50 values were about 1,000 times larger than that of AITC, and their maximal responses were equal. They activated TRPA1 more strongly than TRPV1. Their EC50 values for TRPV1 were 2 times larger, and the maximal response was less than half of that for TRPA1. Next, we studied the potencies of other lipid components for both receptors. Most of them have higher affinity to TRPA1 than TRPV1. Among them, dicarboxylic acids showed equal efficacy for both receptors, but those are present in only small amounts in RJ. We concluded that the main function of RJ is TRPA1 activation by HDEA and HDAA, the major components of the RJ lipid fraction.