Su Jie, Cheng Fuyu, Yuan Wei
Department of Cardiology, Hospital of Jiangsu University, Zhenjiang, China.
The British Heart Foundation Centre of Excellence, St Thomas' Hospital, School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, The Rayne Institute, London, United Kingdom.
Front Med (Lausanne). 2024 Nov 28;11:1512916. doi: 10.3389/fmed.2024.1512916. eCollection 2024.
The cyclic GMP-AMP synthase (cGAS) and its downstream effector, the stimulator of interferon genes (STING), are crucial components of the innate immune response, traditionally recognized for their role in detecting cytosolic DNA from pathogens and damaged host cells. However, recent research indicates that the cGAS-STING pathway also significantly impacts metabolic processes, particularly glycerolipid metabolism. Glycerolipids are essential for energy storage and cellular membrane integrity, and their dysregulation is linked to metabolic disorders such as obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). Both cGAS and STING are expressed in various metabolic tissues, suggesting a potential role in lipid homeostasis. Chronic activation of the cGAS-STING pathway may promote inflammatory states that exacerbate insulin resistance and lipid accumulation, forming a feedback loop of metabolic dysfunction. This review explores the emerging relationship between cGAS/STING signaling and glycerolipid metabolism, discussing the mechanisms through which this pathway influences lipid regulation and the potential for therapeutic interventions. By integrating insights from immunology and metabolism, we aim to provide a comprehensive understanding of how the cGAS-STING axis may serve as a novel target for addressing metabolic disorders and enhancing metabolic health outcomes.
环鸟苷酸-腺苷酸合成酶（cGAS）及其下游效应分子干扰素基因刺激因子（STING）是先天性免疫反应的关键组成部分，传统上认为它们在检测来自病原体和受损宿主细胞的胞质DNA方面发挥作用。然而，最近的研究表明，cGAS-STING通路也对代谢过程有显著影响，尤其是甘油脂质代谢。甘油脂质对于能量储存和细胞膜完整性至关重要，其失调与肥胖、胰岛素抵抗和非酒精性脂肪性肝病（NAFLD）等代谢紊乱有关。cGAS和STING在各种代谢组织中均有表达，提示其在脂质稳态中可能发挥作用。cGAS-STING通路的慢性激活可能会促进炎症状态，加剧胰岛素抵抗和脂质积累，形成代谢功能障碍的反馈回路。本综述探讨了cGAS/STING信号与甘油脂质代谢之间新出现的关系，讨论了该通路影响脂质调节的机制以及治疗干预的潜力。通过整合免疫学和代谢学的见解，我们旨在全面了解cGAS-STING轴如何作为解决代谢紊乱和改善代谢健康结果的新靶点。
