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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 10
Oct.  2019
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Article Contents

Research advances in the role and mechanism of peroxisome proliferator-activated receptor alpha in liver diseases

DOI: 10.3969/j.issn.1001-5256.2019.10.049
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  • Received Date: 2019-05-08
  • Published Date: 2019-10-20
  • Peroxisome proliferator-activated receptor alpha(PPARα) is a member of the nuclear receptor superfamily and plays a central regulatory role in lipid metabolism. Recent studies have found that PPARα agonists play a key role in the prevention and treatment of nonalcoholic fatty liver disease,which has also been reported in other liver diseases. This article reviews the role and mechanism of PPARα in nonalcoholic fatty liver disease,alcoholic liver disease,viral hepatitis,cholestatic liver disease,drug-induced liver injury,and hepatocellular carcinoma,so as to provide a reference for the research on the new application of conventional drugs associated with PPARα.

     

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  • [1] D'SOUZA AA,DEVARAJAN PV. Asialoglycoprotein receptor mediated hepatocyte targeting-strategies and applications[J]. J Control Release,2015,203:126-139.
    [2] FRUCHART JC. Peroxisome proliferator-activated receptoralpha(PPARalpha):At the crossroads of obesity,diabetes and cardiovascular disease[J]. Atherosclerosis,2009,205(1):1-8.
    [3] RAKHSHANDEHROO M,KNOCH B,MULLER M,et al. Peroxisome proliferator-activated receptor alpha target genes[J]. PPAR Res,2010,2010:pii 612089.
    [4] IP E,FARRELL GC,ROBERTSON G,et al. Central role of PPARalpha-dependent hepatic lipid turnover in dietary steatohepatitis in mice[J]. Hepatology,2003,38(1):123-132.
    [5] DONG TS,JACOBS JP. Nonalcoholic fatty liver disease and the gut microbiome:Are bacteria responsible for fatty liver?[J]. Exp Biol Med(Maywood):2019,244(6):408-418..
    [6] 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.
    [7] YANG X,FU Y,HU F,et al. PIK3R3 regulates PPARalpha expression to stimulate fatty acid beta-oxidation and decrease hepatosteatosis[J]. Exp Mol Med,2018,50(1):e431.
    [8] ZHAI X,CHEN X,LU J,et al. Hydrogen-rich saline improves nonalcoholic fatty liver disease by alleviating oxidative stress and activating hepatic PPARalpha and PPARgamma[J]. Mol Med Rep,2017,15(3):1305-1312.
    [9] REN T,ZHU J,ZHU L,et al. The combination of blueberry juice and probiotics ameliorate non-alcoholic steatohepatitis(NASH)by affecting SREBP-1c/PNPLA-3 pathway via PPAR-alpha[J]. Nutrients,2017,9(3):e198.
    [10] CHEN J,LIU J,WANG Y,et al. Wogonin mitigates nonalcoholic fatty liver disease via enhancing PPARalpha/AdipoR2,in vivo and in vitro[J]. Biomed Pharmacother,2017,91:621-631.
    [11] LI TT,TAN TB,HOU HQ,et al. Changes in peroxisome proliferator-activated receptor alpha target gene expression in peripheral blood mononuclear cells associated with non-alcoholic fatty liver disease[J]. Lipids Health Dis,2018,17(1):256-263.
    [12] FRANCQUE S,VERRIJKEN A,CARON S,et al. PPARalpha gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis[J]. J Hepatol,2015,63(1):164-173.
    [13] RATZIU V,HARRISON SA,FRANCQUE S,et al. Elafibranor,an agonist of the peroxisome proliferator-activated receptor-αand-δ,induces resolution of nonalcoholic steatohepatitis without fibrosis worsening[J]. Gastroenterology,2016,150(5):1147-1159. e5.
    [14] NANJI AA,DANNENBERG AJ,JOKELAINEN K,et al. Alcoholic liver injury in the rat is associated with reduced expression of peroxisome proliferator-alpha(PPARalpha)-regulated genes and is ameliorated by PPARalpha activation[J]. J Pharmacol and Exp Ther,2004,310(1):417-424.
    [15] FISCHER M,YOU M,MATSUMOTO M,et al. Peroxisome proliferator-activated receptor alpha(PPARalpha)agonist treatment reverses PPARalpha dysfunction and abnormalities in hepatic lipid metabolism in ethanol-fed mice[J]. J Biol Chem,2003,278(30):27997-8004.
    [16] LI JL,WANG QY,LUAN HY,et al. Effects of L-carnitine against oxidative stress in human hepatocytes:Involvement of peroxisome proliferator-activated receptor alpha[J]. J Biomed Sci,2012,19:32-40.
    [17] NAN YM,KONG LB,REN WG,et al. Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol mediated liver fibrosis in mice[J]. Lipids Health Dis,2013,12:11-20.
    [18] HUANG YC,LIU KC,CHIOU YL,et al. Fenofibrate suppresses melanogenesis in B16-F10 melanoma cells via activation of the p38 mitogen-activated protein kinase pathway[J].Chem Biol Interact,2013,205(3):157-164.
    [19] KONG L,REN W,LI W,et al. Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol induced steatohepa titis in mice[J]. Lipids Health Dis,2011,10:246.
    [20] MCBRIDE G. Hepatitis B virus-induced liver cancer in Asian Americans:A preventable disease[J]. J Natl Cancer Inst,2008,100(8):528-529.
    [21] DU L,MA Y,LIU M,et al. Peroxisome proliferators activated receptor(PPAR)agonists activate hepatitis B virus replication in vivo[J]. Virol J,2017,14(1):96-104.
    [22] DHARANCY S,MALAPEL M,PERLEMUTER G,et al. Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection[J]. Gastroenterology,2005,128(2):334-342.
    [23] READ SA,TAY ES,SHAHIDI M,et al. The mechanism of interferon refractoriness during hepatitis C virus infection and its reversal with a peroxisome proliferator-activated receptor alpha agonist[J]. J Interferon Cytokine Res,2015,35(6):488-497.
    [24] YU YC,CHEN CW. Current status and research interests of the diagnosis and treatment of cholestatic liver disease[J]. J Clin Hepatol,2019,35(2):241-246.(in Chinese)于乐成,陈成伟.胆汁淤积性肝病的诊治现状及研究方向[J].临床肝胆病杂志,2019,35(2):241-246.
    [25] HUA J,NI QQ. Progress in drug treatment of cholestatic liver disease[J]. J Intern Med Concepts Pract,2018,13(6):334-338.(in Chinese)华静,倪茜茜.胆汁淤积性肝病的药物治疗进展[J].内科理论与实践,2018,13(6):334-338.
    [26] ZHANG L,FAN YJ,TAN B,et al. Recognition of the clinical application and biological mechanism of ursodeoxycholic acid in liver diseases[J]. Chin J Clin Pharmacol Ther,2017,22(2):233-240.(in Chinese)张林林,樊玉娟,谭波,等.熊脱氧胆酸在慢性肝病中应用及机制的再认识[J].中国临床药理学与治疗学,2017,22(2):233-240.
    [27] DAI M,YANG J,XIE M,et al. Inhibition of JNK signalling mediates PPARα-dependent protection against intrahepatic cholestasis by fenofibrate[J]. Br J Pharmacol,2017,174(18):3000-3017.
    [28] GHONEM NS,ASSIS DN,BOYER JL. Fibrates and cholestasis[J]. Hepatology,2015,62(2):635-643.
    [29] GHONEM NS,ANANTHANARAYANAN M,SOROKA CJ,et al.Peroxisome proliferator-activated receptorαactivates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion[J]. Hepatology,2014,59(3):1030-1042.
    [30] ZHU H,ZHAO YL,ZHAO QG,et al. Mechanism and clinical effect of fibrates in treatment of primary biliary cirrhosis[J].Evaluat Anal Drug-Use Hosp China,2017,17(1):10-12.(in Chinese)朱红,赵艳玲,赵庆国,等.贝特类药物治疗原发性胆汁性肝硬化的机制和疗效[J].中国医院用药评价与分析,2017,17(1):10-12.
    [31] WEI XC,CHEN F,HAN XW. Acute cholestasis-type liver damage induced by fenofibrate:A case report[J]. Chin Hosp Pharm J,2019,39(3):319-320.(in Chinese)魏晓晨,陈凡,韩晓文.非诺贝特致急性胆汁淤积型肝损害1例[J].中国医院药学杂志,2019,39(3):319-320.
    [32] LIU A,KRAUSZ KW,FANG ZZ,et al. Gemfibrozil disrupts lysophosphatidylcholine and bile acid homeostasis via PPARαand its relevance to hepatotoxicity[J]. Arch Toxicol,2014,88(4):983-996.
    [33] HAJDU D,AIGLOVK,VINKLEROVI,et al. Acute cholestatic hepatitis induced by fenofibrate[J]. J Clin Pharm Ther,2009,34(5):599-602.
    [34] FONTANA RJ,WATKINS PB,BONKOVSKY HL,et al. Drug-induced liver injury network(DILIN)prospective study:Rationale,design and conduct[J]. Drug Saf,2009,32(1):55-68.
    [35] HAQUE T,SASATOMI E,HAYASHI PH. Drug-induced liver injury:Pattern recognition and future directions[J]. Gut Liver,2016,10(1):27-36.
    [36] ZHAO XQ,DONG J. Clinical features and CT imaging findings of drug-induced liver injury[J]. Chin J CT MRI,2019,17(3):83-86.(in Chinese)赵向前,董菁.药物性肝损伤患者的临床特点及CT影像学表现分析[J].中国CT和MRI杂志,2019,17(3):83-86.
    [37] ZHANG Y,PAN Y,XIONG R,et al. FGF21 mediates the protective effect of fenofibrate against acetaminophen-induced hepatotoxicity via activating autophagy in mice[J]. Biochem Biophys Res Commun,2018,503(2):474-481.
    [38] MINATA M,HARADA KH,KRRMAN A,et al. Role of peroxisome proliferator-activated receptor-alpha in hepatobiliary injury induced by ammonium perfluorooctanoate in mouse liver[J]. Ind Health,2010,48(1):96-107.
    [39] ZHANG Y,GUO H,HASSAN HM,et al. Pyrazinamide induced hepatic injury in rats through inhibiting the PPARαpathway[J]. J Appl Toxicol,2016,36(12):1579-1590.
    [40] HEDRINGTON MS,DAVIS SN. Peroxisome proliferator-activated receptor alpha-mediated drug toxicity in the liver[J].Expert Opin Drug Metab Toxicol,2018,14(7):671-677.
    [41] EL-SERAG HB,RUDOLPH KL. Hepatocellular carcinoma:epidemiology and molecular carcinogenesis[J]. Gastroenterology,2007,7(132):2557-2576.
    [42] ZHAO H,ZOU LW,ZHENG SS,et al. Association between the NQO1 C609T polymorphism with hepatocellular carcinoma risk in the Chinese population[J]. Asian Pac J Cancer Prev,2015,16(5):1821-1825.
    [43] LIAN X,WANG G,ZHOU H,et al. Anticancer properties of fenofibrate:A repurposing use[J]. J Cancer,2018,9(9):1527-1537.
    [44] XIAO YB,CAI SH,LIU LL,et al. Decreased expression of peroxisome proliferator-activated receptor alpha indicates unfavorable outcomes in hepatocellular carcinoma[J]. Cancer Manag Res,2018,10:1781-1789.
    [45] PINEDA TORRA I,GERVOIS P,STAELS B. Peroxisome proliferator-activated receptor alpha in metabolic disease,inflammation,atherosclerosis and aging[J]. Curr Opin Lipidol,1999,10(2):151-159.
    [46] TANAKA N,MORIYA K,KIYOSAWA K,et al. PPARalpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice[J]. J Clin Invest,2008,118(2):683-694.
    [47] MASAOMI K. Hepatocarcinogenic susceptibility of fenofibrate and its possible mechanism of carcinogenicity in a two-stage hepatocarcinogenesis model of rasH2 mice[J]. Toxicol Pathol,2008,36(7):950-957.
    [48] NISHIMURA J,DEWA Y,OKAMURA T,et al. Possible involvement of oxidative stress in fenofibrate-induced hepatocarcinogenesis in rats[J]. Arch Toxicol,2008,82(9):641-654.
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