Desat1-mediated lipid homeostasis mitigates 20E-induced lipotoxicity in blood-fed mosquitoes

Peilu Sun, Guandong Wang, Bingchen Yang, Yiguan Wang, Chunlai Cui, Ling Dong, Yifei Li, Tao Zhou, Fang Li and Sibao Wang ()
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Peilu Sun: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Guandong Wang: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Bingchen Yang: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Yiguan Wang: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Chunlai Cui: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Ling Dong: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Yifei Li: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Tao Zhou: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Fang Li: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology
Sibao Wang: Chinese Academy of Sciences, New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Adequate lipid storage capacity is crucial for animal reproductive success, especially in female mosquitoes, which must accumulate sufficient lipid reserves to support egg production. However, the molecular mechanisms regulating lipid accumulation and the consequences of inadequate lipid stores remain poorly understood. Here, we show that stearoyl-CoA desaturase 1 (desat1) is indispensable for lipid reserve establishment and metabolic balance in female Anopheles and Aedes mosquitoes. Knockdown of desat1 of newly emerged females results in high mortality following a blood meal, whereas silencing desat1 of older mosquitoes does not affect survival. Moreover, desat1 activity of early-emerged females is essential for egg production and peritrophic matrix integrity. Lipidomic analyses reveal that silencing desat1 impairs the conversion of saturated fatty acids (SFAs) to unsaturated fatty acids (USFAs), disrupting triglyceride synthesis and leading to SFA accumulation. After blood feeding, accumulated SFAs induce lipotoxicity, characterized by elevated oxidative stress and apoptosis. We further find that blood meal-derived proteins stimulate the 20-hydroxyecdysone (20E) signaling pathway, thereby exacerbating fatty acid β-oxidation, increasing reactive oxygen species (ROS) production, and inducing extensive apoptotic cell death in desat1-silenced early-emerged females, ultimately leading to mortality. Our findings reveal Desat1 as a critical metabolic safeguard against hormone-induced lipotoxicity in blood-feeding insects, establishing a novel mechanistic link between classical lipid metabolism and steroid hormone signaling, and identifying desat1 as a promising target for vector control strategies.

Date: 2025
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DOI: 10.1038/s41467-025-65407-6

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