College of Pharmacy, Pusan National University, Busan, 46214, Republic of Korea.
Arch Pharm Res. 2021 Oct;44(9-10):839-856. doi: 10.1007/s12272-021-01352-4. Epub 2021 Oct 18.
Fibrosis is defined by abnormal accumulation of extracellular matrix, which can affect virtually every organ system under diseased conditions. Fibrotic tissue remodeling often leads to organ dysfunction and is highly associated with increased morbidity and mortality. The disease burden caused by fibrosis is substantial, and the medical need for effective antifibrotic therapies is essential. Significant progress has been made in understanding the molecular mechanism and pathobiology of fibrosis, such as transforming growth factor-β (TGF-β)-mediated signaling pathways. However, owing to the complex and dynamic properties of fibrotic disorders, there are currently no therapeutic options that can prevent or reverse fibrosis. Recent studies have revealed that alterations in fatty acid metabolic processes are common mechanisms and core pathways that play a central role in different fibrotic disorders. Excessive lipid accumulation or defective fatty acid oxidation is associated with increased lipotoxicity, which directly contributes to the development of fibrosis. Genetic alterations or pharmacologic targeting of fatty acid metabolic processes have great potential for the inhibition of fibrosis development. Furthermore, mechanistic studies have revealed active interactions between altered metabolic processes and fibrosis development. Several well-known fibrotic factors change the lipid metabolic processes, while altered metabolic processes actively participate in fibrosis development. This review summarizes the recent evidence linking fatty acid metabolism and fibrosis, and provides new insights into the pathogenesis of fibrotic diseases for the development of drugs for fibrosis prevention and treatment.
纤维化是由细胞外基质的异常积累定义的，它几乎可以在患病条件下影响所有器官系统。纤维组织重塑通常会导致器官功能障碍，并且与发病率和死亡率的增加高度相关。纤维化引起的疾病负担很大，因此对有效抗纤维化治疗的医疗需求至关重要。在理解纤维化的分子机制和病理生物学方面已经取得了重大进展，例如转化生长因子-β（TGF-β）介导的信号通路。然而，由于纤维化疾病的复杂和动态特性，目前尚无能够预防或逆转纤维化的治疗选择。最近的研究表明，脂肪酸代谢过程的改变是不同纤维化疾病中发挥核心作用的常见机制和核心途径。过多的脂质积累或脂肪酸氧化缺陷与脂毒性增加有关，这直接导致纤维化的发展。脂肪酸代谢过程的遗传改变或药物靶向具有抑制纤维化发展的巨大潜力。此外，机制研究揭示了代谢过程的改变与纤维化发展之间的积极相互作用。几种已知的纤维化因子改变脂质代谢过程，而改变的代谢过程则积极参与纤维化的发展。这篇综述总结了脂肪酸代谢与纤维化之间的最新证据，并为纤维化疾病的发病机制提供了新的见解，以期开发出预防和治疗纤维化的药物。
