>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
细胞胆固醇稳态失衡在非酒精性脂肪性肝病中的作用研究进展
作者:吴娱1  马坤岭2 
单位:1. 东南大学 医学院, 江苏 南京 210009;
2. 东南大学附属中大医院 肾内科, 江苏 南京 210009
关键词:非酒精性脂肪性肝病 游离胆固醇 胆固醇稳态 文献综述 
分类号:R575.5
出版年·卷·期(页码):2014·33·第六期(778-782)
摘要:

游离胆固醇(FC)的沉积可以直接损伤肝细胞,通过破坏线粒体和内质网(ER)膜的完整性,触发线粒体氧化损伤以及ER应激,同时促进有毒的羟胆固醇产生,直接诱导脂肪组织功能紊乱.肝细胞胆固醇稳态失衡,包括胆固醇内流增加、外流减少以及肠肝循环障碍都参与了非酒精性脂肪性肝病(NAFLD)的发病机制.通过药物来纠正胆固醇稳态失调将开启治疗NAFLD的新篇章.

参考文献:

[1] MUSSO G,GAMBINO R,CASSADER M,et al.Meta-analysis: natural history of non-alcoholic fatty liver disease(NAFLD)and diagnostic accuracy of non-invasive tests for liver disease severity[J].Ann Med,2011,43(8): 617-649.
[2] TILG H,MOSCHEN A R.Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis[J].Hepatology,2010,52(5): 1836-1846.
[3] NEUSCHWANDER-TETRI B A.Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites[J].Hepatology,2010,52(2): 774-788.
[4] TABAS I.Consequences of cellular cholesterol accumulation: basic concepts and physiological implications[J].J Clin Invest,2002,110(7): 905-911.
[5] MONTERO J,MARI M,COLELL A,et al.Cholesterol and peroxidized cardiolipin in mitochondrial membrane properties,permeabilization and cell death[J].Biochim Biophys Acta,2010,1797(6): 1217-1224.
[6] MEI S,GU H,YANG X,et al.Prolonged exposure to insulin induces mitochondrion-derived oxidative stress through increasing mitochondrial cholesterol content in hepatocytes[J].Endocrinology,2012,153(5): 2120-2129.
[7] FU S,WATKINS S M,HOTAMISLIGIL G S.The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling[J].Cell Metab,2012,15(5): 623-634.
[8] FERRÉN,MARTÍNEZ-CLEMENTE M,LPEZ-PARRA M,et al.Increased susceptibility to exacerbated liver injury in hypercholesterolemic ApoE-deficient mice: potential involvement of oxysterols[J].Am J Physiol Gastrointest Liver Physiol,2009,296(3): G553-G562.
[9] GARENC C,JULIEN P,LEVY E.Oxysterols in biological systems: the gastrointestinal tract,liver,vascular wall and central nervous system[J].Free Radic Res,2009,44(1): 47-73.
[10] XU L,BAI Q,RODRIGUEZ-AGUDO D,et al.Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate[J].Lipids,2010,45(9): 821-832.
[11] YOU Q,CHENG L,KEDL R M,et al.Mechanism of T cell tolerance induction by murine hepatic Kupffer cells[J].Hepatology,2008,48(3): 978-990.
[12] MUSSO G,GAMBINO R,PACINI G,et al.Prolonged saturated fat-induced,glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver[J].Am J Clin Nutr,2009,89(2): 558-567.
[13] TERATANI T,TOMITA K,SUZUKI T,et al.A high-cholesterol diet exacerbates liver fibrosis in mice via accumulation of free cholesterol in hepatic stellate cells[J].Gastroenterology,2012,142(1): 152-164.
[14] MUSSO G,CASSADER M,de MICHIELI F,et al.Effect of lectin-like oxidized LDL receptor-1 polymorphism on liver disease,glucose homeostasis,and postprandial lipoprotein metabolism in nonalcoholic steatohepatitis[J].Am J Clin Nutr,2011,94(4): 1033-1042.
[15] PILCH P F,MESHULAM T,DING S,et al.Caveolae and lipid trafficking in adipocytes[J].Clin Lipidol,2011,6(1): 49-58.
[16] HAILSTONES D,SLEER L S,PARTON R G,et al.Regulation of caveolin and caveolae by cholesterol in MDCK cells[J].J Lipid Res,1998,39(2): 369-379.
[17] van ROOYEN D M,LARTER C Z,HAIGH W G,et al.Hepatic free cholesterol accumulates in obese,diabetic mice and causes nonalcoholic steatohepatitis[J].Gastroenterology,2011,141(4): 1393-1403.
[18] ZHAO L,CHEN Y,TANG R,et al.Inflammatory stress exacerbates hepatic cholesterol accumulation via increasing cholesterol uptake and de novo synthesis[J].J Gastroenterol Hepatol,2011,26(5): 875-883.
[19] BELLIA A,RIZZA S,LOMBARDO M F,et al.Deterioration of glucose homeostasis in type 2 diabetic patients one year after beginning of statins therapy[J].Atherosclerosis,2012,223(1): 197-203.
[20] MUSSO G,CASSADER M,BO S,et al.Sterol regulatory element-binding factor 2(SREBF-2)predicts 7-year NAFLD incidence and severity of liver disease and lipoprotein and glucose dysmetabolism[J].Diabetes,2013,62(4): 1109-1120.
[21] CABALLERO F,FERNNDEZ A,de LACY A M,et al.Enhanced free cholesterol,SREBP-2 and StAR expression in human NASH[J].J Hepatol,2009,50(4): 789-796.
[22] 汪蕾,陈红霞,陈莉,等.不同他汀类药物治疗兔心肌缺血再灌注损伤的疗效及机制探讨[J].现代医学,2013,41(2): 81-84.
[23] CLARK B J.The mammalian START domain protein family in lipid transport in health and disease[J].J Endocrinol,2012,212(3): 257-275.
[24] MONTERO J,MORALES A,LLACUNA L,et al.Mitochondrial cholesterol contributes to chemotherapy resistance in hepatocellular carcinoma[J].Cancer Res,2008,68(13): 5246-5256.
[25] PEAKE K B,VANCE J E.Defective cholesterol trafficking in Niemann-Pick C-deficient cells[J].FEBS Letters,2010,584(13): 2731-2739.
[26] MITRO N,MAK P A,VARGAS L,et al.The nuclear receptor LXR is a glucose sensor[J].Nature,2007,445(7124): 219-223.
[27] JELINEK D,MILLWARD V,BIRDI A,et al.Npc1 haploinsufficiency promotes weight gain and metabolic features associated with insulin resistance[J].Hum Mol Genet,2011,20(2): 312-321.
[28] JANSEN M,OHSAKI Y,RITA-REGA L,et al.Role of ORPs in sterol transport from plasma membrane to ER and lipid droplets in mammalian cells[J].Traffic,2011,12(2): 218-231.
[29] ZHOU T,LI S,ZHONG W,et al.OSBP-related protein 8(ORP8)regulates plasma and liver tissue lipid levels and interacts with the nucleoporin Nup62[J].PLoS One,2011,6(6): e21078.
[30] SU K,SABEVA N S,LIU J,et al.The ABCG5 ABCG8 sterol transporter opposes the development of fatty liver disease and loss of glycemic control independently of phytosterol accumulation[J].J Biol Chem,2012,287(34): 28564-28575.
[31] ADORINI L,PRUZANSKI M,SHAPIRO D.Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis[J].Drug Discov Today,2012,17(17): 988-997.
[32] KONG B,LUYENDYK J P,TAWFIK O,et al.Farnesoid X receptor deficiency induces nonalcoholic steatohepatitis in low-density lipoprotein receptor-knockout mice fed a high-fat diet[J].J Pharmacol Exp Ther,2009,328(1): 116-122.
[33] ZELCER N,HONG C,BOYADJIAN R,et al.LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor[J].Science,2009,325(5936): 100-104.
[34] WOUTERS K,BILSEN M,GORP P J,et al.Intrahepatic cholesterol influences progression,inhibition and reversal of non-alcoholic steatohepatitis in hyperlipidemic mice[J].FEBS Letters,2010,584(5): 1001-1005.
[35] LIU Y,QIU D K,MA X.Liver X receptors bridge hepatic lipid metabolism and inflammation[J].J Dig Dis,2012,13(2): 69-74.
[36] ALGER H M,BROWN J M,SAWYER J K,et al.Inhibition of acyl-coenzyme A: cholesterol acyltransferase 2(ACAT2)prevents dietary cholesterol-associated steatosis by enhancing hepatic triglyceride mobilization[J].J Biol Chem,2010,285(19): 14267-14274.
[37] JIA L,BETTERS J L,YU L.Niemann-pick C1-like 1(NPC1L1) protein in intestinal and hepatic cholesterol transport[J].Annu Rev Physiol,2011,73: 239-259.
[38] LABONTÉE D,CAMAROTA L M,ROJAS J C,et al.Reduced absorption of saturated fatty acids and resistance to diet-induced obesity and diabetes by ezetimibe-treated and Npc111-/-mice[J].Am J Physiol Gastrointest Liver Physiol,2008,295(4): G776.
[39] 钟勇,江时森,王俊,等.依折麦布对db/db糖尿病小鼠胰岛自身胰岛素信号通路的影响[J].东南大学学报: 医学版,2014,33(1): 54-58.
[40] TANG W,JIA L,MA Y,et al.Ezetimibe restores biliary cholesterol excretion in mice expressing Niemann-Pick C1-Like 1 only in liver[J].Biochim Biophys Acta,2011,1811(9): 549-555.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 414641 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-83272481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364