自噬相关信号分子在非酒精性脂肪性肝病中的作用

贺晶霞; 安秀琴; 刘近春

doi:10.3969/j.issn.1001-5256.2021.09.044

自噬相关信号分子在非酒精性脂肪性肝病中的作用

DOI: 10.3969/j.issn.1001-5256.2021.09.044

1.
山西医科大学研究生院, 太原 030001
2.
山西医科大学第一医院消化内科, 太原 030001

基金项目:

山西省科技成果转化引导专项项目 (201904D131030)

利益冲突声明: 所有作者均声明不存在利益冲突。

作者贡献声明: 贺晶霞负责收集文献, 撰写论文；安秀琴负责修改论文；刘近春负责拟定写作思路、指导撰写文章、最后定稿及经费支持。

详细信息

通信作者:
刘近春, zxr610624@163.com

中图分类号: R575.5
计量
- 文章访问数: 709
- HTML全文浏览量: 87
- PDF下载量: 32
- 被引次数: 0
出版历程
- 收稿日期: 2021-01-17
- 录用日期: 2021-03-08
- 出版日期: 2021-09-20

Research advances in autophagy-related signal molecules in nonalcoholic fatty liver disease

1.
Graduate School of Shanxi Medical University, Taiyuan 030001, China
2.
Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China

Research funding:

Transformation of Scientific and Technological Achievements Special Guide Project of Shanxi Province (201904D131030)

摘要

摘要: 非酒精性脂肪性肝病已成为世界范围内慢性肝病的主要原因之一, 与代谢综合征关系密切。近年来, 非酒精性脂肪性肝病的发病机制研究的越来越深入, 其中, 自噬是真核生物体内一个高度保守的过程, 在非酒精性脂肪性肝病的疾病进展中起着至关重要的作用, 有望成为治疗非酒精性脂肪性肝病的新靶标。就自噬相关信号分子在非酒精性脂肪性肝病中的研究进展进行综述, 以期为治疗非酒精性脂肪性肝病提供新思路。
- 非酒精性脂肪性肝病 /
- 自噬 /
- 信号传导
Abstract: Nonalcoholic fatty liver disease (NAFLD) has become one of the main causes of chronic liver diseases worldwide and is closely associated with metabolic syndrome. In-depth studies on the pathogenesis of NAFLD in recent years have shown that autophagy is a highly conservative process in eukaryotes and plays an important role in the progression of NAFLD, and therefore, it is expected to become a new target for the treatment of NAFLD. This article reviews the research advances in autophagy-related signal molecules in NAFLD, in order to provide new ideas for the treatment of NAFLD.
- Non-alcoholic Fatty Liver Disease /
- Autophagy /
- Signal Transduction

HTML全文

参考文献(48)

[1]	YOUNOSSI ZM, NOUREDDIN M, BERNSTEIN D, et al. Role of noninvasive tests in clinical gastroenterology practices to identify patients with nonalcoholic steatohepatitis at high risk of adverse outcomes: Expert panel recommendations[J]. Am J Gastroenterol, 2021, 116(2): 254-262. DOI: 10.14309/ajg.0000000000001054.
[2]	GE X, ZHENG L, WANG M, et al. Prevalence trends in non-alcoholic fatty liver disease at the global, regional and national levels, 1990-2017: A population-based observational study[J]. BMJ Open, 2020, 10(8): e036663. DOI: 10.1136/bmjopen-2019-036663.
[3]	YOUNOSSI ZM. Non-alcoholic fatty liver disease - A global public health perspective[J]. J Hepatol, 2019, 70(3): 531-544. DOI: 10.1016/j.jhep.2018.10.033.
[4]	DAY CP, JAMES OF. Steatohepatitis: A tale of two "hits"?[J]. Gastroenterology, 1998, 114(4): 842-845. DOI: 10.1016/s0016-5085(98)70599-2.
[5]	LIU Q, NIU CY. From "two hit theory" to "multiple hit theory": Implications of evolution of pathogenesis concepts for treatment of non-alcoholic fatty liver disease[J]. World Chin J Dig, 2019, 27 (19): 1171-1178. DOI: 10.11569/wcjd.v27.i19.1171. 刘勤, 牛春燕. 由"二次打击"到"多重打击": 发病机制的演变带给非酒精性脂肪性肝病的治疗启示[J]. 世界华人消化杂志, 2019, 27(19): 1171-1178. DOI: 10.11569/wcjd.v27.i19.1171.
[6]	UDRISTIOIU A, NICA-BADEA D. Autophagy dysfunctions associated with cancer cells and their therapeutic implications[J]. Biomed Pharmacother, 2019, 115: 108892. DOI: 10.1016/j.biopha.2019.108892.
[7]	WESSELBORG S, STORK B. Autophagy signal transduction by ATG proteins: From hierarchies to networks[J]. Cell Mol Life Sci, 2015, 72(24): 4721-4757. DOI: 10.1007/s00018-015-2034-8.
[8]	CASARES-CRESPO L, CALATAYUD-BASELGA I, GARCÍA-CORZO L, et al. On the role of basal autophagy in adult neural stem cells and neurogenesis[J]. Front Cell Neurosci, 2018, 12: 339. DOI: 10.3389/fncel.2018.00339.
[9]	SAITO T, KUMA A, SUGIURA Y, et al. Autophagy regulates lipid metabolism through selective turnover of NCoR1[J]. Nat Commun, 2019, 10(1): 1567. DOI: 10.1038/s41467-019-08829-3.
[10]	DUAN NN, LIU XJ, WU J. Palmitic acid elicits hepatic stellate cell activation through inflammasomes and hedgehog signaling[J]. Life Sci, 2017, 176: 42-53. DOI: 10.1016/j.lfs.2017.03.012.
[11]	LI XQ, WANG W, JIA YH, et al. Autophagy and nonalcoholic fatty liver disease[J]. Chin J Hepatol, 2016, 24(8): 632-635. DOI: 10.3760/cma.j.issn.1007-3418.2016.08.016. 李相迁, 王玮, 贾艳红, 等. 细胞自噬与非酒精性脂肪性肝病[J]. 中华肝脏病杂志, 2016, 24(8): 632-635. DOI: 10.3760/cma.j.issn.1007-3418.2016.08.016.
[12]	YAN H, GAO Y, ZHANG Y. Inhibition of JNK suppresses autophagy and attenuates insulin resistance in a rat model of nonalcoholic fatty liver disease[J]. Mol Med Rep, 2017, 15(1): 180-186. DOI: 10.3892/mmr.2016.5966.
[13]	KE PY. Diverse functions of autophagy in liver physiology and liver diseases[J]. Int J Mol Sci, 2019, 20(2). DOI: 10.3390/ijms20020300.
[14]	QIAN Y, LI M, WANG W, et al. Effects of lactobacillus casei YBJ02 on lipid metabolism in hyperlipidemic mice[J]. J Food Sci, 2019, 84(12): 3793-3803. DOI: 10.1111/1750-3841.14787.
[15]	CHEN M, LIU J, YANG L, et al. AMP-activated protein kinase regulates lipid metabolism and the fibrotic phenotype of hepatic stellate cells through inhibition of autophagy[J]. FEBS Open Bio, 2017, 7(6): 811-820. DOI: 10.1002/2211-5463.12221.
[16]	ZHAO Z, WANG C, ZHANG L, et al. Lactobacillus plantarum NA136 improves the non-alcoholic fatty liver disease by modulating the AMPK/Nrf2 pathway[J]. Appl Microbiol Biotechnol, 2019, 103(14): 5843-5850. DOI: 10.1007/s00253-019-09703-4.
[17]	XIAO WS, LE YY, ZENG SL, et al. Research advances in the pathogenesis of nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36(8): 1874-1879. DOI: 10.3969/j.issn.1001-5256.2020.08.043. 肖伟松, 乐滢玉, 曾胜澜, 等. 非酒精性脂肪性肝病的发病机制研究进展[J]. 临床肝胆病杂志, 2020, 36(8): 1874-1879. DOI: 10.3969/j.issn.1001-5256.2020.08.043.
[18]	DEBOSCH BJ, HEITMEIER MR, MAYER AL, et al. Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis[J]. Sci Signal, 2016, 9(416): ra21. DOI: 10.1126/scisignal.aac5472.
[19]	ALLAIRE M, RAUTOU PE, CODOGNO P, et al. Autophagy in liver diseases: Time for translation?[J]. J Hepatol, 2019, 70(5): 985-998. DOI: 10.1016/j.jhep.2019.01.026.
[20]	HE Q, SHA S, SUN L, et al. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway[J]. Biochem Biophys Res Commun, 2016, 476(4): 196-203. DOI: 10.1016/j.bbrc.2016.05.086.
[21]	JUNG CH, JUN CB, RO SH, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery[J]. Mol Biol Cell, 2009, 20(7): 1992-2003. DOI: 10.1091/mbc.e08-12-1249.
[22]	WANG H, LIU Y, WANG D, et al. The upstream pathway of mTOR-mediated autophagy in liver diseases[J]. Cells, 2019, 8(12): 1597. DOI: 10.3390/cells8121597.
[23]	THELEN AM, ZONCU R. Emerging roles for the lysosome in lipid metabolism[J]. Trends Cell Biol, 2017, 27(11): 833-850. DOI: 10.1016/j.tcb.2017.07.006.
[24]	WANG Y, DING WX, LI T. Cholesterol and bile acid-mediated regulation of autophagy in fatty liver diseases and atherosclerosis[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2018, 1863(7): 726-733. DOI: 10.1016/j.bbalip.2018.04.005.
[25]	PREIDIS GA, KIM KH, MOORE DD. Nutrient-sensing nuclear receptors PPARα and FXR control liver energy balance[J]. J Clin Invest, 2017, 127(4): 1193-1201. DOI: 10.1172/JCI88893.
[26]	LIN P, LU JM, WANG YF, et al. Prevention mechanism of 2, 3, 5, 4'-Tetrahydroxy-stilbene-2-O-β-D-glucoside on lipid accumulation in steatosis hepatic L-02 cell[J]. Pharmacogn Mag, 2017, 13(50): 245-253. DOI: 10.4103/0973-1296.204563.
[27]	LI D, LI YL. Pathogenesis and treatment progress of NAFLD[J]. Pract Pharm Clin Remedies, 2017, 20 (11): 1340-1343. DOI: 10.14053/j.cnki.ppcr.201711029. 李丹, 李异玲. 非酒精性脂肪性肝病发病机制及治疗进展[J]. 实用药物与临床, 2017, 20(11): 1340-1343. DOI: 10.14053/j.cnki.ppcr.201711029.
[28]	YU LN, LIU WY, MA LQ. Research progress on the relationship between TFEB and non-alcoholic fatty liver[J]. Shandong Med J, 2016, 56(42): 106-109. DOI: 10.3969/j.issn.1002-266X.2016.42.038. 余琳娜, 柳唯意, 马岚青. TFEB与非酒精性脂肪肝关系的研究进展[J]. 山东医药, 2016, 56(42): 106-109. DOI: 10.3969/j.issn.1002-266X.2016.42.038.
[29]	KIM SH, KIM G, HAN DH, et al. Ezetimibe ameliorates steatohepatitis via AMP activated protein kinase-TFEB-mediated activation of autophagy and NLRP3 inflammasome inhibition[J]. Autophagy, 2017, 13(10): 1767-1781. DOI: 10.1080/15548627.2017.1356977.
[30]	WANG Y, DING WX, LI T. Cholesterol and bile acid-mediated regulation of autophagy in fatty liver diseases and atherosclerosis[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2018, 1863(7): 726-733. DOI: 10.1016/j.bbalip.2018.04.005.
[31]	ENGIN A. Non-alcoholic fatty liver disease[J]. Adv Exp Med Biol, 2017, 960: 443-467. DOI: 10.1007/978-3-319-48382-5_19.
[32]	SHIH CC, SHLAU MT, LIN CH, et al. Momordica charantia ameliorates insulin resistance and dyslipidemia with altered hepatic glucose production and fatty acid synthesis and AMPK phosphorylation in high-fat-fed mice[J]. Phytother Res, 2014, 28(3): 363-371. DOI: 10.1002/ptr.5003.
[33]	CUI J, SHEN HM, LIM L. The role of autophagy in liver cancer: Crosstalk in signaling pathways and potential therapeutic targets[J]. Pharmaceuticals (Basel), 2020, 13(12). DOI: 10.3390/ph13120432.
[34]	XIAO Y, LIU H, YU J, et al. MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy[J]. Autophagy, 2016, 12(3): 592-593. DOI: 10.1080/15548627.2015.1135282.
[35]	SOLINAS G, BECATTINI B. JNK at the crossroad of obesity, insulin resistance, and cell stress response[J]. Mol Metab, 2017, 6(2): 174-184. DOI: 10.1016/j.molmet.2016.12.001.
[36]	YAN H, GAO YQ, ZHANG Y, et al. Chlorogenic acid alleviates autophagy and insulin resistance by suppressing JNK pathway in a rat model of nonalcoholic fatty liver disease[J]. J Biosci, 2018, 43(2): 287-294. DOI: 10.1007/s12038-018-9746-5.
[37]	LIU XH, LI L, QI ZH, et al. Farnesoid X receptor is an important target in lipid metabolism[J]. Chin J Clin Pharmacol Ther, 2018, 23(8): 955-960. DOI: 10.12092/j.issn.1009-2501.2018.08.020. 刘晓红, 李玲, 齐振华, 等. 脂质代谢中的重要靶点: 法尼酯X受体(FXR)[J]. 中国临床药理学与治疗学, 2018, 23(8): 955-960. DOI: 10.12092/j.issn.1009-2501.2018.08.020.
[38]	SHEN C, DOU X, MA Y, et al. Nicotinamide protects hepatocytes against palmitate-induced lipotoxicity via SIRT1-dependent autophagy induction[J]. Nutr Res, 2017, 40: 40-47. DOI: 10.1016/j.nutres.2017.03.005.
[39]	DITTENHAFER-REED KE, RICHARDS AL, FAN J, et al. SIRT3 mediates multi-tissue coupling for metabolic fuel switching[J]. Cell Metab, 2015, 21(4): 637-646. DOI: 10.1016/j.cmet.2015.03.007.
[40]	LI XY, ZHAO ZX, HUANG M, et al. Effect of berberine on promoting the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters[J]. J Transl Med, 2015, 13: 278. DOI: 10.1186/s12967-015-0629-3.
[41]	BYUN S, SEOK S, KIM YC, et al. Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase[J]. Nat Commun, 2020, 11(1): 807. DOI: 10.1038/s41467-020-14384-z.
[42]	SHI Q, PEI F, SILVERMAN GA, et al. Mechanisms of action of autophagy modulators dissected by quantitative systems pharmacology analysis[J]. Int J Mol Sci, 2020, 21(8): 2855. DOI: 10.3390/ijms21082855.
[43]	LI T, WEN L, CHENG B. Cordycepin alleviates hepatic lipid accumulation by inducing protective autophagy via PKA/mTOR pathway[J]. Biochem Biophys Res Commun, 2019, 516(3): 632-638. DOI: 10.1016/j.bbrc.2019.06.108.
[44]	KIM B, LEE Y, CHOI H, et al. The trehalose-6-phosphate phosphatase Tps2 regulates ATG8 transcription and autophagy in Saccharomyces cerevisiae[J]. Autophagy, 2021, 17(4): 1013-1027. DOI: 10.1080/15548627.2020.1746592.
[45]	WU D, ZHONG P, WANG Y, et al. Hydrogen sulfide attenuates high-fat diet-induced non-alcoholic fatty liver disease by inhibiting apoptosis and promoting autophagy via reactive oxygen species/phosphatidylinositol 3-Kinase/AKT/Mammalian target of rapamycin signaling pathway[J]. Front Pharmacol, 2020, 11: 585860. DOI: 10.3389/fphar.2020.585860.
[46]	SPORMANN L, RENNERT C, KOLBE E, et al. Cyclopamine and rapamycin synergistically inhibit mTOR signalling in mouse hepatocytes, revealing an interaction of Hedgehog and mTOR signalling in the liver[J]. Cells, 2020, 9(8): 1817. DOI: 10.3390/cells9081817.
[47]	COCHRANE CR, VAGHJIANI V, SZCZEPNY A, et al. Trp53 and Rb1 regulate autophagy and ligand-dependent Hedgehog signaling[J]. J Clin Invest, 2020, 130(8): 4006-4018. DOI: 10.1172/JCI132513.
[48]	National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association; Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: A 2018 update[J]. J Clin Hepatol, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007. 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.