Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, China.
Cell Mol Life Sci. 2024 Mar 8;81(1):120. doi: 10.1007/s00018-024-05131-4.
Reputable evidence from multiple studies suggests that excessive and uncontrolled inflammation plays an indispensable role in mediating, amplifying, and protracting acute lung injury (ALI). Traditionally, immunity and energy metabolism are regarded as separate functions regulated by distinct mechanisms, but recently, more and more evidence show that immunity and energy metabolism exhibit a strong interaction which has given rise to an emerging field of immunometabolism. Mammalian lungs are organs with active fatty acid metabolism, however, during ALI, inflammation and oxidative stress lead to a series metabolic reprogramming such as impaired fatty acid oxidation, increased expression of proteins involved in fatty acid uptake and transport, enhanced synthesis of fatty acids, and accumulation of lipid droplets. In addition, obesity represents a significant risk factor for ALI/ARDS. Thus, we have further elucidated the mechanisms of obesity exacerbating ALI from the perspective of fatty acid metabolism. To sum up, this paper presents a systematical review of the relationship between extensive fatty acid metabolic pathways and acute lung injury and summarizes recent advances in understanding the involvement of fatty acid metabolism-related pathways in ALI. We hold an optimistic believe that targeting fatty acid metabolism pathway is a promising lung protection strategy, but the specific regulatory mechanisms are way too complex, necessitating further extensive and in-depth investigations in future studies.
有大量研究提供了可靠证据，表明过度和失控的炎症在介导、放大和延长急性肺损伤（ALI）方面起着不可或缺的作用。传统上，免疫和能量代谢被认为是由不同机制调节的独立功能，但最近越来越多的证据表明，免疫和能量代谢之间存在强烈的相互作用，这引发了一个新兴的免疫代谢领域。哺乳动物的肺是具有活跃脂肪酸代谢的器官，但在 ALI 中，炎症和氧化应激会导致一系列代谢重编程，如脂肪酸氧化受损、参与脂肪酸摄取和转运的蛋白质表达增加、脂肪酸合成增强以及脂滴积累。此外，肥胖是 ALI/ARDS 的一个重要危险因素。因此，我们从脂肪酸代谢的角度进一步阐明了肥胖加重 ALI 的机制。总之，本文系统地综述了广泛的脂肪酸代谢途径与急性肺损伤之间的关系，并总结了近年来对脂肪酸代谢相关途径参与 ALI 的认识进展。我们乐观地认为，靶向脂肪酸代谢途径是一种有前途的肺保护策略，但具体的调节机制过于复杂，需要在未来的研究中进行更广泛和深入的探索。
