Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity
Yu‑Jie Mou1,2 · Hai‑Yue Tu3 · Yi‑Chan Wang1,2 · Shao‑Yong Song1,2 · Hua‑Yue Liu1,2,4 · Dong Wang5 · Jun‑Chao Wu6 · Xiao‑Wen Meng1,2 · Zheng‑Hong Qin6,7 · Fu‑Hai Ji1,2
1 Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
2 Present Address: Institute of Anesthesiology, Soochow University, Suzhou 215006, China
3 Present Address: Institutes for Translational Medicine, Suzhou Medical College of Soochow University, Suzhou 215123, China
4 Ambulatory Surgery Center, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
5 Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
6 Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
7 Institute of Health Science and Technology, Suzhou GaoBo Vocational College, Suzhou 215163, China
Abstract
Anesthetics are indispensable in clinical practice, yet growing evidence indicates that they can disrupt brain function beyond their intended effects. While research on anesthetic neurotoxicity has largely focused on neurons, microglia are now recognized as central players in determining perioperative outcomes. Lipid metabolism in microglia has emerged as a key regulator of immune responses, synaptic maintenance, and neuroinflammation. Anesthetic exposure disturbs this metabolic balance, leading to lipid droplet accumulation, defective fatty acid oxidation, and pro-inflammatory activation that contribute to cognitive impairment. However, knowledge in this field remains fragmented and has not been systematically synthesized. In this review, we integrate current evidence on how anesthetics perturb microglial lipid metabolism and delineate the mechanistic pathways involved, with the goal of identifying potential therapeutic targets related to microglial lipid metabolism to alleviate anesthesia neurotoxicity.
Keywords
Lipid metabolism; Microglia; Anesthetic neurotoxicity; Cognitive dysfunction; Lipid-targeted therapy
