Tarsal lipids regulate xenobiotic penetration in Drosophila melanogaster

Insects touch their proximal environment with their tarsi. The immediate contact with xenobiotics occurs with the tarsal cuticle surface that is covered with cuticular hydrocarbons (CHCs). In this work, we tested the hypothesis that xenobiotics entry through the tarsi depended on CHC amounts and composition. Applying RNA interference, we suppressed the expression of genes coding for the key enzymes of CHC production Cyp4G1 (total CHC), desat1 (unsaturated CHCs) and FASN2 (branched CHCs) in lipid producing oenocytes and analyzed the penetration efficiency of the insecticides DDT and chlorantraniliprole and of the inert dye Eosin Y in the respective flies. As expected, in walking experiments, reduction of CHC amounts (cyp4G1^RNAi) enhanced insecticide and dye penetration into the tarsi. In the same assay, we identified unsaturated CHCs as the main CHC component attenuating DDT and chlorantraniliprole at low concentrations. Likewise, tarsal adhesion and uptake of Eosin Y depended rather on unsaturated than on branched CHCs. Extrapolating from our data, we propose a two-step model of xenobiotics penetration through the tarsal cuticle: first, modulated by unsaturated CHCs, the molecule is repelled or adheres to the cuticle surface; upon adhesion, the molecule penetrates the cuticle and accumulates in the tarsal lumen in a second step. Whether these mechanisms apply to molecules other than Eosin Y remains to be investigated. Taken together, the tarsal cuticle constitutes a selective bipartite barrier against uncontrolled uptake of contact xenobiotics.