Developmental blue-light exposure alters glucose and lipid metabolism through a ROS-ACD-1-associated oxidized-lipid pathway in C. elegans.

Although light broadly affects animal physiology, it remains unclear whether specific wavelengths directly reshape basal glucose and lipid metabolism in developing non-visual photoreceptive animals, and what specific molecular pathways mediate these effects. Here, using Caenorhabditis elegans (C. elegans), a model lacking visual organs but retaining conserved metabolic pathways, we systematically evaluated metabolic phenotypes following early-life (L1 to young adult) exposure to red, green, blue, and white light spectra. We identified that blue light (450-460 nm) most strongly drove triglyceride accumulation and free glucose elevation, with the L4-to-young adult transition being the most susceptible developmental window. Mechanistically, blue light induced oxidative stress and mitochondrial dysfunction; antioxidants limited glucose and lipid abnormalities and reshaped physiology, establishing a functional role for ROS. Integrated multi-omics revealed that elevated ROS upregulated the DEG/ENaC family channel acd-1 and promoted the accumulation of an oxidized lipid metabolite feature putatively annotated as 12(13)Ep-9-KODE (EKODE), which was functionally evaluated as a candidate downstream oxidized lipid mediator associated with ACD-1-dependent metabolic remodeling. Moreover, chemically induced oxidative stress similarly upregulated both acd-1 mRNA expression and the abundance of this EKODE-annotated oxidized-lipid feature. Notably, in mammalian cells, overexpression of the human homolog ASIC4 or exogenous EKODE supplementation recapitulated key metabolic features, including lipid-droplet accumulation, triglyceride elevation, and coordinated bioenergetic remodeling. Together, our findings support a ROS-dependent ACD-1-associated oxidized lipid regulatory module in C. elegans and reveal how early-life blue light and oxidative challenges influence metabolic homeostasis.