Apolipoprotein D neofunctionalization couples lipid allocation to wing evolution

The origin of insect wings marked a pivotal evolutionary innovation that enabled their extraordinary ecological success, yet the metabolic mechanisms sustaining this transition remain elusive. Here, we identify apolipoprotein D2 (ApoD2)-a neofunctionalized paralog of apolipoprotein D-as a key metabolic regulator that spatially coordinates lipid allocation during lepidopteran wing development. Comparative phylogenomics across 791 metazoan genomes revealed that ApoD2 emerged as a lepidopteran duplicate exhibiting sustained, wing-enriched expression across developmental stages. Using Bombyx mori as a model, we show that ApoD2 is indispensable for wing morphogenesis, coupling lipid compartmentalization to local energetic demands. Loss of ApoD2 disrupts mitochondrial bioenergetics and fatty acid oxidation, leading to depletion of wing muscle cells. Lipidomic profiling further revealed that ApoD2 deficiency causes systemic lipid misallocation-characterized by hemolymph fatty acid accumulation and depletion of diglycerides and morphogenic lipids in wings, triggering AMPK-dependent autophagy. Mechanistically, duplicated ApoD2 integrates systemic lipid transport with organ-specific energy deployment, linking metabolic rewiring to morphological innovation. Together, these findings reveal how the neofunctionalization of a metabolic regulator resolved evolutionary trade-offs between energy efficiency and structural complexity, illuminating a general principle by which metabolic innovation drives the evolution of complex traits in insects.