ACSL1促进肝脏脂质积累与炎症发生并参与疾病发展的研究进展

Advances in studies on ACSL1’s promoting hepatic lipid accumulation and inflammation and participating in disease development

长链脂酰辅酶A合成酶(acyl-CoA synthetase long-chain,ACSL)属于多基因家族编码的酶,位于内质网和线粒体外膜上的ACSL主要催化脂肪酸形成脂酰辅酶A(acyl-CoA),参与脂肪酸代谢、膜修饰等多种生理过程。ACSL家族在不同细胞的脂肪酸代谢中发挥不同作用,其功能异常可导致如脂肪肝、动脉粥样硬化和糖尿病的发生。ACSL家族成员1(ACSL family member 1,ACSL1)作为ACSL家族在肝脏中的主要亚型,主要参与维持胆固醇稳定、脂肪酸活化以及胆汁酸代谢,同时与某些肝脏疾病如肝细胞癌、非酒精性脂肪肝的发生发展密切相关。本文综述了ACSL家族各成员的生理功能、作用特点,并阐释了ACSL1对脂质代谢、调节细胞铁死亡的影响以及在相关疾病如肝纤维化、肝细胞癌、恶病质、非酒精性脂肪肝、甲状腺癌以及乳腺癌发展中的作用机制的研究进展。

The acyl-CoA synthetase long-chain(ACSL)belongs to an enzyme encoded by a polygenic family.ACSL,located in the endoplasmic reticulum and outer mitochondrial membrane,can catalyze fatty acids to form acyl-CoA,participating in many physiological processes,such as fatty acid metabolism and membrane modification.The ACSL family plays different roles in the fatty acid metabolism of different cells,and its dysfunction can lead to conditions such as fatty liver,arteriosclerosis,and diabetes.As a major subtype of the ACSL family in the liver,ACSL family member 1(ACSL1)is mainly involved in the maintenance of cholesterol stability,fatty acid activation,and bile acid metabolism.It is also associated with the development of certain liver diseases such as hepatocellular carcinoma and steatosis.This paper reviews differences in physiological functions and functional characteristics of ACSL family members.It also discusses the advances in studies on the role of ACSL1 in influencing lipid metabolism,regulating cellular iron death,and the development of related diseases such as liver fibrosis,hepatocellular carcinoma,cachexia,steatosis,thyroid cancer,and breast cancer.