非酒精性脂肪性肝炎中的自噬作用。
Autophagy in nonalcoholic steatohepatitis.
机构信息
Department of Medicine, Marion Bessin Liver Research Center and Diabetes Research and Training Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
出版信息
Expert Rev Gastroenterol Hepatol. 2011 Apr;5(2):159-66. doi: 10.1586/egh.11.4.
Abstract
Autophagy is a critical pathway for the degradation of intracellular components by lysosomes. Established functions for both macroautophagy and chaperone-mediated autophagy in hepatic lipid metabolism, insulin sensitivity and cellular injury suggest a number of potential mechanistic roles for autophagy in nonalcoholic steatohepatitis (NASH). Decreased autophagic function in particular may promote the initial development of hepatic steatosis and progression of steatosis to liver injury. Additional functions of autophagy in immune responses and carcinogenesis may also contribute to the development of NASH and its complications. The impairment in autophagy that occurs with cellular lipid accumulation, obesity and aging may therefore have an important impact on this disease, and agents to augment hepatic autophagy have therapeutic potential in NASH.
摘要
自噬是溶酶体降解细胞内成分的关键途径。在肝内脂质代谢、胰岛素敏感性和细胞损伤中，巨自噬和伴侣介导的自噬的既定功能表明自噬在非酒精性脂肪性肝炎（NASH）中有许多潜在的机制作用。特别是自噬功能的降低可能会促进肝脂肪变性的最初发展，并使脂肪变性向肝损伤进展。自噬在免疫反应和致癌作用中的其他功能也可能导致 NASH 的发展及其并发症。因此，随着细胞脂质积累、肥胖和衰老而发生的自噬损伤可能对这种疾病有重要影响，并且增强肝自噬的药物在 NASH 中有治疗潜力。
相似文献
1
Autophagy in nonalcoholic steatohepatitis.非酒精性脂肪性肝炎中的自噬作用。
Expert Rev Gastroenterol Hepatol. 2011 Apr;5(2):159-66. doi: 10.1586/egh.11.4.
2
Comprehensive study of the interplay between immunological and metabolic factors in hepatic steatosis.全面研究肝脂肪变性中免疫和代谢因素的相互作用。
Int Immunopharmacol. 2024 May 30;133:112091. doi: 10.1016/j.intimp.2024.112091. Epub 2024 Apr 23.
3
Molecular Mechanisms: Connections between Nonalcoholic Fatty Liver Disease, Steatohepatitis and Hepatocellular Carcinoma.分子机制：非酒精性脂肪性肝病、脂肪性肝炎和肝细胞癌之间的联系。
Int J Mol Sci. 2020 Feb 23;21(4):1525. doi: 10.3390/ijms21041525.
4
Immunological and molecular basis of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease.非酒精性脂肪性肝炎和非酒精性脂肪性肝病的免疫和分子基础。
Expert Rev Clin Immunol. 2013 Aug;9(8):727-38. doi: 10.1586/1744666X.2013.816484.
5
Gemcabene downregulates inflammatory, lipid-altering and cell-signaling genes in the STAM™ model of NASH.Gemcabene 下调 STAM™ 模型中 NASH 的炎症、脂质改变和细胞信号基因。
PLoS One. 2018 May 30;13(5):e0194568. doi: 10.1371/journal.pone.0194568. eCollection 2018.
6
The ménage à trois of autophagy, lipid droplets and liver disease.自噬、脂滴与肝脏疾病的三者关系。
Autophagy. 2022 Jan;18(1):50-72. doi: 10.1080/15548627.2021.1895658. Epub 2021 Apr 2.
7
Emerging Roles of T Cells in the Pathogenesis of Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma.T 细胞在非酒精性脂肪性肝炎和肝细胞癌发病机制中的新作用。
Front Endocrinol (Lausanne). 2021 Oct 28;12:760860. doi: 10.3389/fendo.2021.760860. eCollection 2021.
8
Macrophages and scavenger receptors in obesity-associated non-alcoholic liver fatty disease (NAFLD).肥胖相关性非酒精性肝脂肪病（NAFLD）中的巨噬细胞和清道夫受体。
Scand J Immunol. 2020 Nov;92(5):e12971. doi: 10.1111/sji.12971. Epub 2020 Sep 21.
9
Autophagy and the unfolded protein response shape the non-alcoholic fatty liver landscape: decoding the labyrinth.自噬和未折叠蛋白反应塑造非酒精性脂肪肝景观：解读迷宫。
Metabolism. 2024 May;154:155811. doi: 10.1016/j.metabol.2024.155811. Epub 2024 Feb 2.
10
Iron overload in nonalcoholic steatohepatitis.非酒精性脂肪性肝炎中的铁过载。
Adv Clin Chem. 2011;55:105-32. doi: 10.1016/b978-0-12-387042-1.00006-x.
引用本文的文献
1
Melanocortin 3 receptor regulates hepatic autophagy and systemic adiposity.黑皮质素3受体调节肝脏自噬和全身肥胖。
Nat Commun. 2025 Feb 16;16(1):1690. doi: 10.1038/s41467-025-56936-1.
2
Lipotoxicity of palmitic acid is associated with DGAT1 downregulation and abolished by PPARα activation in liver cells.棕榈酸的脂毒性与二酰甘油酰基转移酶1（DGAT1）下调有关，且在肝细胞中通过过氧化物酶体增殖物激活受体α（PPARα）激活可消除该脂毒性。
J Lipid Res. 2024 Dec;65(12):100692. doi: 10.1016/j.jlr.2024.100692. Epub 2024 Nov 5.
3
Hepatokines and MASLD: The GLP1-Ras-FGF21-Fetuin-A Crosstalk as a Therapeutic Target.肝分泌因子与 MASLD：GLP1-Ras-FGF21-胎球蛋白 A 串扰作为治疗靶点。
Int J Mol Sci. 2024 Oct 8;25(19):10795. doi: 10.3390/ijms251910795.
4
Nonalcoholic Fatty Liver Disease and Staging of Hepatic Fibrosis.非酒精性脂肪性肝病与肝纤维化分期。
Adv Exp Med Biol. 2024;1460:539-574. doi: 10.1007/978-3-031-63657-8_18.
5
Autophagy and hepatic lipid metabolism: mechanistic insight and therapeutic potential for MASLD.自噬与肝脏脂质代谢：非酒精性脂肪性肝病的机制洞察与治疗潜力
NPJ Metab Health Dis. 2024;2(1):19. doi: 10.1038/s44324-024-00022-5. Epub 2024 Aug 2.
6
Post-Liver Transplant Metabolic Syndrome.肝移植后代谢综合征
J Clin Exp Hepatol. 2024 Jul-Aug;14(4):101368. doi: 10.1016/j.jceh.2024.101368. Epub 2024 Feb 29.
7
Global research status and frontiers on autophagy in hepatocellular carcinoma: a comprehensive bibliometric and visualized analysis.全球肝细胞癌自噬研究现状与前沿：一项综合的文献计量学和可视化分析。
Int J Surg. 2024 May 1;110(5):2788-2802. doi: 10.1097/JS9.0000000000001202.
8
Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets.脂滴调控的脂噬和伴侣介导的自噬在非酒精性脂肪肝病发病机制中的作用。
Int J Mol Sci. 2023 Nov 2;24(21):15891. doi: 10.3390/ijms242115891.
9
Chaperone-mediated autophagy: Molecular mechanisms, biological functions, and diseases.伴侣蛋白介导的自噬：分子机制、生物学功能及相关疾病
MedComm (2020). 2023 Aug 30;4(5):e347. doi: 10.1002/mco2.347. eCollection 2023 Oct.
10
The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting.热量限制和禁食诱导自噬的有益和有害作用。
Adv Nutr. 2023 Sep;14(5):1211-1225. doi: 10.1016/j.advnut.2023.07.006. Epub 2023 Jul 30.
本文引用的文献
1
Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice.自噬可减轻小鼠急性乙醇诱导的肝毒性和脂肪变性。
Gastroenterology. 2010 Nov;139(5):1740-52. doi: 10.1053/j.gastro.2010.07.041. Epub 2010 Jul 23.
2
Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistance to oxidant stress.自噬和伴侣蛋白介导的自噬对于肝细胞抵抗氧化应激是必需的。
Hepatology. 2010 Jul;52(1):266-77. doi: 10.1002/hep.23645.
3
Regulation of innate immune responses by autophagy-related proteins.自噬相关蛋白对固有免疫反应的调节。
J Cell Biol. 2010 Jun 14;189(6):925-35. doi: 10.1083/jcb.201002021.
4
Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity.细胞质 FoxO1 对于自噬的诱导和肿瘤抑制活性是必不可少的。
Nat Cell Biol. 2010 Jul;12(7):665-75. doi: 10.1038/ncb2069. Epub 2010 Jun 13.
5
An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis.一种自噬增强药物可促进突变型α1-抗胰蛋白酶 Z 的降解，减少肝纤维化。
Science. 2010 Jul 9;329(5988):229-32. doi: 10.1126/science.1190354. Epub 2010 Jun 3.
6
Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance.肥胖导致的肝脏自噬缺陷会促进内质网应激，并引起胰岛素抵抗。
Cell Metab. 2010 Jun 9;11(6):467-78. doi: 10.1016/j.cmet.2010.04.005.
7
Altered lipid content inhibits autophagic vesicular fusion.脂质含量的改变会抑制自噬囊泡融合。
FASEB J. 2010 Aug;24(8):3052-65. doi: 10.1096/fj.09-144519. Epub 2010 Apr 7.
8
Chaperone-mediated autophagy: molecular mechanisms and physiological relevance.伴侣蛋白介导的自噬：分子机制与生理相关性。
Semin Cell Dev Biol. 2010 Sep;21(7):719-26. doi: 10.1016/j.semcdb.2010.02.005. Epub 2010 Feb 20.
9
Autophagy in health and disease. 2. Regulation of lipid metabolism and storage by autophagy: pathophysiological implications.自噬在健康和疾病中的作用。2. 自噬对脂质代谢和储存的调节：病理生理学意义。
Am J Physiol Cell Physiol. 2010 May;298(5):C973-8. doi: 10.1152/ajpcell.00527.2009. Epub 2010 Jan 20.
10
Autophagy in health and disease. 1. Regulation and significance of autophagy: an overview.自噬在健康和疾病中的作用。1. 自噬的调控和意义：概述。
Am J Physiol Cell Physiol. 2010 Apr;298(4):C776-85. doi: 10.1152/ajpcell.00507.2009. Epub 2010 Jan 20.
Zotero 插件