肝X受体在非酒精性脂肪性肝病中的作用

李文秘; 王楠; 边倩; 黄倩; 李京涛; 魏海梁; 闫曙光

doi:10.3969/j.issn.1001-5256.2020.10.041

肝X受体在非酒精性脂肪性肝病中的作用

DOI: 10.3969/j.issn.1001-5256.2020.10.041

1. 陕西中医药大学第一临床医学院
2. 陕西中医药大学附属医院

基金项目:

国家自然科学基金(81603612)；陕西省重点研发计划(2020ZDLSF05-15)；陕西省科技厅基金(2018KJXX-093)；国家级和陕西省大学生创新创业训练计划项目(201810716023,201831023)；陕西中医药大学学科创新团队建设项目(2019-YL05)；

详细信息

中图分类号: R575.5
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出版历程
- 收稿日期: 2020-04-21
- 出版日期: 2020-10-20

Role of liver X receptor in nonalcoholic fatty liver disease

The First Clinical Medical College,Shaanxi University of Chinese Medicine
The Affiliated Hospital of Shaanxi University of Chinese Medicine

Research funding:

摘要

摘要: 脂质过量沉积、肝损伤、胰岛素抵抗是非酒精性脂肪性肝病发生发展进程中的标志性特征。肝X受体(LXR)作为DNA转录调节因子,其两种细胞亚型LXRα和LXRβ在调节胆固醇代谢、诱导抗炎和减轻胰岛素抵抗中发挥着关键作用。综述了LXR的结构、功能,LXR与NAFLD发病机制的关系,为NAFLD的预防和治疗提供新思路和新方法。
- 非酒精性脂肪性肝病 /
- 肝X受体 /
- 胆固醇
Abstract: Excessive lipid deposition,liver injury,and insulin resistance are hallmarks in the development and progression of nonalcoholic fatty liver disease( NAFLD). Liver X receptor( LXR) is a transcriptional regulator,and its two cell subtypes,LXRα and LXRβ,play a key role in regulating cholesterol metabolism,inducing anti-inflammation,and reducing insulin resistance. This article reviews the structure and function of LXR and its association with the pathogenesis of NAFLD,in order to provide new ideas and methods for the prevention and treatment of NAFLD.
- non-alcoholic fatty liver disease /
- liver X receptors /
- cholesterol

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参考文献(36)

[1] 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.(in Chinese)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.

[2] YOUNOSSI Z,TACKE F,ARRESE M,et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Hepatology,2019,69(6):2672-2682.

[3] DUC D,VIGNE S,POT C. Oxysterols in autoimmunity[J]. Int J Mol Sci,2019,20(18):4522.

[4] MA Z,DENG C,HU W,et al. Liver X receptors and their agonists:Targeting for cholesterol homeostasis and cardiovascular diseases[J]. Curr Issues Mol Biol,2017,22:41-64.

[5] HIEBL V,LADURNER A,LATKOLIK S,et al. Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR[J]. Biotechnol Adv,2018,36(6):1657-1698.

[6] MOHAMMAD MB,SAEIDEH ZK,SOHRAB H,et al. ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production,insulin-glucose homeostasis,in flammation and obesity[J]. Diabetes Metab Syndr,2019,13(2):1529-1534.

[7] HARRIS MT,HUSSAIN SS,INOUYE CM,et al. Reinterpretation of the localization of the ATP binding cassette transporter ABCG1 in insulin-secreting cells and insights regarding its trafficking and function[J]. PLo S One, 2018, 13(9):e0198383.

[8] ZEIN AA,KAUR R,HUSSEIN T,et al. ABCG5/G8:A structural view to pathophysiology of the hepatobiliary cholesterol secretion[J]. Biochem Soc Trans,2019,47(5):1259-1268.

[9] TOYODA Y,TAKADA T,YAMANASHI Y,et al. Pathophysiological importance of bile cholesterol reabsorption:Hepatic NPC1L1-exacerbated steatosis and decreasing VLDL-TG secretion in mice fed a high-fat diet[J]. Lipids Health Dis,2019,18(1):234.

[10] KOMATI R,SPADONI D,ZHENG S,et al. Ligands of therapeutic utility for the liver X receptors[J]. Molecules,2017,22(1):88.

[11] WANG B,TONTONOZ P. Liver X receptors in lipid signalling and membrane homeostasis[J]. Nat Rev Endocrinol,2018,14(8):452-463.

[12] ORAM JF,HEINECKE JW. ATP binding cassette transporter A1:A cell cholesterol exporter that protects against cardiovascular disease[J]. Physiol Rev,2005,85(4):1343-1372.

[13] BANNO A,WANG J,OKADA K,et al. Identification of a novel cholesterol-lowering dipeptide, phenylalanine-proline(FP),and its down-regulation of intestinal ABCA1 in hypercholesterolemic rats and Caco-2 cells[J]. Sci Rep,2019,9(1):19416.

[14] VINCENT V,THAKKAR H,AGGARWAL S,et al. ATP-binding cassette transporter A1(ABCA1)expression in adipose tissue and its modulation with insulin resistance in obesity[J].Diabetes Metab Syndr Obes,2019,12:275-284.

[15] MARANGHI M,TRUGLIO G,GALLO A,et al. A novel splicing mutation in the ABCA1 gene,causing Tangier disease and familial HDL deficiency in a large family[J]. Biochem Biophys Res Commun,2019,508(2):487-493.

[16] EBNER L,GLSER A,BRUER A,et al. Evaluation of two liver treatment strategies in a mouse model of niemann-pick-disease type C1[J]. Int J Mol Sci,2018,19(4):972.

[17] WANG X,COLLINS HL,RANALLETTA M,et al. Macrophage ABCA1 and ABCG1,but not SR-BI,promote macrophage reverse cholesterol transport in vivo[J]. J Clin Invest,2007,117(8):2216-2224.

[18] YU L,YORK J,von BERGMANN K,et al. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATPbinding cassette transporters G5 and G8[J]. J Biol Chem,2003,278(18):15565-15570.

[19] TANG W,JIA L,MA Y,et al. Ezetimibe restores biliary cholesterol excretion in mice expressing Niemann-Pick C1-Like1 only in liver[J]. Biochim Biophys Acta,2011,1811(9):549-555.

[20] RAMN-VZQUEZ A,de LA ROSA JV,TABRAUE C,et al.Common and differential transcriptional actions of nuclear receptors liver X receptorsαandβin macrophages[J]. Mol Cell Biol,2019,39(5):e00376-18.

[21] BEI C,RUN-BIN S,GENG Y,et al. Berberine reverses LPSinduced repression of CYP7A1 through an anti-inflammatory effect[J]. Chin Herb Med,2019,11(3):292-298.

[22] WANG YY,DAHLE MK,AGREN J,et al. Activation of the liver X receptor protects against hepatic injury in endotoxemia by suppressing Kupffer cell activation[J]. Shock,2006,25(2):141-146.

[23] ARCHER A,LAURENCIKIENE J,AHMED O,et al. Skeletal muscle as a target of LXR agonist after long-term treatment:Focus on lipid homeostasis[J]. Am J Physiol Endocrinol Metab,2014,306(5):e494-e502.

[24] LIU Y,HAN X,BIAN Z,et al. Activation of liver X receptors attenuates endotoxin-induced liver injury in mice with nonalcoholic fatty liver disease[J]. Dig Dis Sci,2012,57(2):390-398.

[25] MUSSO G,GAMBINO R,CASSADER M. Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis[J]. Prog Lipid Res,2013,52(1):175-191.

[26] TALL AR,YVAN-CHARVET L. Cholesterol,inflammation and innate immunity[J]. Nat Rev Immunol,2015,15(2):104-116.

[27] NI M,ZHANG B,ZHAO J,et al. Biological mechanisms and related natural modulators of liver X receptor in nonalcoholic fatty liver disease[J]. Biomed Pharmacother,2019,113:108778.

[28] AYAKA I,CYNTHIA H,RONG X,et al. LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling[J]. Elife,2015,4:e08009.

[29] ANTOINE J,THIBAUT B,LOUISE M,et al. Revisiting the role of LXRs in PUFA metabolism and phospholipid homeostasis[J]. Int J Mol Sci,2019,20(15):3787-3797.

[30] GAO MM,LIU DX. The liver X receptor agonist T0901317 protects mice from high fat diet-induced obesity and insulin resistance[J]. AAPS J,2013,15(1):258-266.

[31] KNUT TD,STINE MU,KRISTER B,et al. Expression of the insulin-responsive glucose transporter GLUT4 in adipocytes is dependent on liver X receptorα[J]. J Biol Chem,2003,278(48):48283-48291.

[32] BARANOWSKI M,ZABIELSKI P,BACHNIO-ZABIELSKA AU,et al. Insulin-sensitizing effect of LXR agonist T0901317 in high-fat fed rats is associated with restored muscle GLUT4 expression and insulin-stimulated AS160 phosphorylation[J]. Cell Physiol Biochem,2014,33(4):1047-1057.

[33] MARYC S,MARKJ H. Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance[J]. Biochem Soc Trans,2008,36(Pt 5):891-900.

[34] DONG Y,GAO GR,FAN HY,et al. Activation of the liver X receptor by agonist TO901317 improves hepatic insulin resistance via suppressing reactive oxygen species and JNK pathway[J]. PLo S One,2015,10(4):e0124778.

[35] PETTERSSON AML,STENSON BM,LORENTE CS,et al. LXR is a negative regulator of glucose uptake in human adipocytes[J]. Diabetologia,2013,56(9):2044-2054.

[36] KAORI EU,MAKOTO M,Liver X receptors regulate cholesterol metabolism and immunity in hepatic nonparenchymal cells[J]. Int J Mol Sci,2019,20(20):5045-5061.

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