Carbendazim disrupts cellular lipid homeostasis and induces fat accumulation by upregulation of Δ9-desaturases in Caenorhabditis elegans

Carbendazim (CBZ), a broad-spectrum benzimidazole fungicide, is widely detected in agricultural environments, raising concerns about its potential toxicity to organisms. However, the specific molecular mechanisms, particularly the genetic regulators and downstream metabolic effectors, that drive this disruption are still poorly defined. Combining targeted genetic analysis in Caenorhabditis elegans ( C. elegans ) with non-targeted lipidomics, we demonstrate that CBZ induces substantial lipid accumulation and 1 μg/L CBZ performed at the most by evaluating the Oil Red O staining, triglyceride (TG) and non-esterified fatty acid (NEFA). Targeted genetic analysis and transcriptional analysis uncovered that this metabolic disruption requires the insulin-like receptor daf-2 and aak-2 , and further CBZ specifically and consistently upregulates the Δ9-desaturases, most prominently fat-6 and fat-7 , identifying them as the key effector enzymes. Moreover, untargeted lipidomic revealed that this was characterized by triacylglycerol (TAG) accumulation and a significant enrichment in glycerophospholipid metabolism. Integrated correlation analysis further mapped these key lipid species to two antagonistic transcriptional programs, including a catabolic state linked to atgl-1 and an anabolic state linked to the fat-6 and fat-7 . This study elucidates a novel pathway for fungicide-induced metabolic dysfunction, demonstrating how CBZ hijacks the host metabolic network to drive fat storage through specific desaturase-dependent reprogramming, with potential implications for environmental and human health risk assessment.