Ionotropic receptors mediate arachidic acid perception and food avoidance behavior in Drosophila melanogaster

Chemosensory functions are essential for animals to distinguish between nutritious and harmful compounds. Fatty acids are vital dietary components, but their taste perception mechanisms remain poorly understood. In Drosophila melanogaster, we identified a cluster of ionotropic receptors (IR7g, IR25a, IR51b, IR67a, and IR76b) that mediate the detection of the long-chain saturated fatty acid, arachidic acid (ARCH), through bitter-sensing gustatory receptor neurons. Our findings demonstrate that high doses of ARCH elicit strong aversive responses and exhibit toxic effects, decreasing survival rates in a dose-dependent manner. ARCH detection was found to require the activation of bitter-sensing gustatory receptor neurons, and the inhibition of sugar-sensing neurons contributed to diminished feeding responses. This study provides critical insights into the molecular and neural mechanisms underlying fatty acid perception in Drosophila, opening new avenues for understanding how animals manage dietary lipid intake and its implications for health.