Role and potential significance of peroxisome proliferator-activated receptors in liver diseases

Shuaixia FENG; Ying XU; Han HAN

doi:10.3969/j.issn.1001-5256.2023.07.034

Volume 39 Issue 7

Jul. 2023

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2023 > 39(7): 1747-1753

PDF( 1940 KB)

Role and potential significance of peroxisome proliferator-activated receptors in liver diseases

DOI: 10.3969/j.issn.1001-5256.2023.07.034

Shuaixia FENG,
Ying XU^{,
,},
Han HAN^{,
,}

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Research funding:

National Natural Science Foundation (82173946);

Shanghai Natural Science Foundation of China (21ZR1460500);

Youth Project of National Natural Science Foundation of China (82004162);

Shanghai Youth Science and Technology Talents Sail Program (20yf1449500)

More Information

Corresponding author: XU Ying, xuying.911@163.com (ORCID: 0000-0002-4645-3094); HAN Han, pashanhan@126.com (ORCID: 0000-0001-6454-876X)
Received Date: 2022-10-09
Accepted Date: 2022-11-11
Published Date: 2023-07-20

Abstract

Abstract

Peroxisome proliferator-activated receptors (PPAR) are members of the nuclear estrogen receptor family, and they are involved in a variety of physiological and pathological processes in the human body and play important roles in cellular metabolism, inflammation, and cancer. At present, there are three known subtypes of PPAR, i.e., α, β/δ, and γ. Studies have shown that PPARs are highly expressed in the liver and are widely involved in various physiological and pathological activities such as liver energy metabolism, oxidative stress, and inflammation, and they are also closely associated with the progression of liver diseases. This article reviews the role of PPAR in common liver diseases such as viral hepatitis, metabolic associated fatty liver disease, cholestatic liver disease, liver fibrosis, and primary liver cancer, and the current status of their application in the treatment of liver diseases.
- Peroxisome Proliferator-Activated Receptors,
- Liver Diseases,
- Inflammation

FullText(HTML)

References(50)

References

[1]	WU JY, GAO JM, GONG QH. Advances in effect of peroxisome roliferators-activated receptors inischemic stroke[J]. Chin Pharmacol Bull, 2022, 38(5): 655-659. DOI: 10.12360/CPB202104086. 吴玉佳, 高健美, 龚其海. 过氧化物酶体增殖物激活受体PPAR在缺血性脑卒中作用的研究进展[J]. 中国药理学通报, 2022, 38(5): 655-659. DOI: 10.12360/CPB202104086.
[2]	WEI SX, SUN H. Action mechanism of peroxisome proliferator-activated receptor agonist in myocardial infarction[J]. Adv Cardiovasc Dis, 2021, 42(12): 1110-1113. DOI: 10.16806/j.cnki.issn.1004-3934.2021.12.013. 魏士雄, 孙赫. 过氧化物酶体增殖物激活受体激动剂在心肌梗死中的作用机制研究进展[J]. 心血管病学进展, 2021, 42(12): 1110-1113. DOI: 10.16806/j.cnki.issn.1004-3934.2021.12.013.
[3]	WU JY, LI LL, LI RH. Association and interaction among TGF-β/Wnt-β-catenin/PPARs axis in hypertension and hypertensive trget organ damage[J]. Med Recapitulate, 2021, 27(20): 3969-3976. DOI: 10.3969/j.issn.1006-2084.2021.20.004. 吴佳芸, 李玲玲, 李瑞菡. TGF-β/Wnt-β-catenin/PPARs轴在高血压及其靶器官损害中的关联与交互作用[J]. 医学综述, 2021, 27(20): 3969-3976. DOI: 10.3969/j.issn.1006-2084.2021.20.004.
[4]	XIE BJ, GUO JJ, ZHANG Y. Peroxisome proliferator-activated recrptor alpha regulates HBV minichromosome remodeling and viral replication[J]. J Chongqing Med Univ, 2017, 42(7): 795-802. DOI: 10.13406/j.cnki.cyxb.001349. 谢冰珏, 郭进军, 张燕. 过氧化物酶体增殖物激活受体α(PPARα)调控HBV微染色体重塑与病毒复制[J]. 重庆医科大学学报, 2017, 42(7): 795-802. DOI: 10.13406/j.cnki.cyxb.001349.
[5]	WU XT, YANG J, WANG XJ. Anti-HBV effect ldentification of antisense oligodeoxynucleotide targeting PPARα[J]. Letters in Biotechnol, 2011, 22(6): 773-776. DOI: 10.3969/j.issn.1009-0002.2011.06.005. 吴小桃, 杨静, 王学军. 抑制核转录因子PPARα的反义寡核苷酸的抗乙型肝炎病毒活性研究[J]. 生物技术通讯, 2011, 22(6): 773-776. DOI: 10.3969/j.issn.1009-0002.2011.06.005.
[6]	LIN YM, SUN HY, CHIU WT, et al. Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation[J]. Viruses, 2018, 10(2): 57. DOI: 10.3390/v10020057.
[7]	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. DOI: 10.1053/j.gastro.2004.11.016.
[8]	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. DOI: 10.1172/JCI33594.
[9]	WAKUI Y, INOUE J, UENO Y, et al. Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone[J]. Biochem Biophys Res Commun, 2010, 396(2): 508-514. DOI: 10.1016/j.bbrc.2010.04.128.
[10]	XIAO ZL, ZHENG WB, YANG J, et al. Clinical efficacy of laparoscopic sleeve gastrectomy in treatment of obesity associated nonal-coholic fatty liver disease[J]. Chin J Dig Surg, 2021, 20(9): 988-993. DOI: 10.3760/cma.j.cn115610-20210823-00411. 肖志立, 郑文彬, 杨钧, 等. 腹腔镜袖状胃切除术治疗肥胖症相关非酒精性脂肪性肝病的临床疗效[J]. 中华消化外科杂志, 2021, 20(9): 988-993. DOI: 10.3760/cma.j.cn115610-20210823-00411.
[11]	XIE J, YANG M, XING Y. Effects of liraglutide on glucose and lipid metabolism and insulin resistance in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease[J/CD]. Chin J Liver Dis (Electronic Version), 2021, 13(4): 46-53. DOI: 10.3969/j.issn.1674-7380.2021.04.008. 谢晶, 杨淼, 邢英. 利拉鲁肽对2型糖尿病合并非酒精性脂肪性肝病患者糖脂代谢及胰岛素抵抗的影响[J/CD]. 中国肝脏病杂志(电子版), 2021, 13(4): 46-53. DOI: 10.3969/j.issn.1674-7380.2021.04.008.
[12]	MA HL, QUAN L, JIANG S. Analysis of clinical characteristics and risk factors in patients with nonal-coholic fatty liver disease complicated with type 2 diabetes mellitus[J]. China Med Herald, 2022, 19(21): 70-73, 82. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202221016.htm 马海林, 权莉, 蒋升. 非酒精性脂肪性肝病合并2型糖尿病患者的临床特征及危险因素分析[J]. 中国医药导报, 2022, 19(21): 70-73, 82. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202221016.htm
[13]	LUNDÅSEN T, HUNT MC, NILSSON LM, et al. PPARalpha is a key regulator of hepatic FGF21[J]. Biochem Biophys Res Commun, 2007, 360(2): 437-440. DOI: 10.1016/j.bbrc.2007.06.068.
[14]	HE Y, YANG W, GAN L, et al. Silencing HIF-1α aggravates non-alcoholic fatty liver disease in vitro through inhibiting PPAR-α/ANGPTL4 singling pathway[J]. Gastroenterol Hepatol, 2021, 44(5): 355-365. DOI: 10.1016/j.gastrohep.2020.09.014.
[15]	WEI X, ZHANG J, TANG M, et al. Fat mass and obesity-associated protein promotes liver steatosis by targeting PPARα[J]. Lipids Health Dis, 2022, 21(1): 29. DOI: 10.1186/s12944-022-01640-y.
[16]	LEE HJ, YEON JE, KO EJ, et al. Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2015, 21(45): 12787-12799. DOI: 10.3748/wjg.v21.i45.12787.
[17]	LIU L, YAN HM, ZHANG CZ. Effect of heat-clearing and damp-draining preparation on mRNA expression of PPARα in hepatic tissue of rats with NASH[J]. Inf Tradit Chin Med, 2012, 29(2): 101-104. DOI: 10.3969/j.issn.1002-2406.2012.02.043. 刘林, 严红梅, 张赤志. 非酒精性脂肪性肝炎大鼠肝组织过氧化物酶体增殖物激活受体αmRNA表达及清热化湿法对其影响的实验研究[J]. 中医药信息, 2012, 29(2): 101-104. DOI: 10.3969/j.issn.1002-2406.2012.02.043.
[18]	WEI PG, HUANG J. Effects of PPAR gamma on cholesterol metabolism and metabolism-related genes[J/CD]. J World Latest Med Inf, 2019, 19(26): 110-111. DOI: 10.19613/j.cnki.1671-3141.2019.26.054. 魏鹏歌, 黄健. PPARγ对胆固醇代谢及代谢相关基因的影响[J/CD]. 世界最新医学信息文摘, 2019, 19(26): 110-111. DOI: 10.19613/j.cnki.1671-3141.2019.26.054.
[19]	MA JX, GUO JZ, CHEN HN, et al. Lsoflavones from sojae semen praeparatum regulate lipid metabolism in atherosclerotic mice through PPARγ/LXRα/ABCA1 signaling pathway[J]. Chin J Exp Med Formul, 2022, 28(11): 110-118. DOI: 10.13422/j.cnki.syfjx.20220940. 马晶鑫, 郭金洲, 陈海宁, 等. 淡豆豉异黄酮通过PPARγ/LXRα/ABCA1信号通路改善动脉粥样硬化小鼠脂质代谢的作用[J]. 中国实验方剂学杂志, 2022, 28(11): 110-118. DOI: 10.13422/j.cnki.syfjx.20220940.
[20]	LI Z, HUANG ZS, LI F. Application of fenofibrate and bicyclol combination in treatment of patients with non-alcoholic fatty liver diseases and changes of hepatic PPARγ2[J]. J Pract Hepatol, 2021, 24(1): 59-62. DOI: 10.3969/j.issn.1672-5069.2021.01.016. 李钊, 黄赞松, 李繁. 非诺贝特联合双环醇治疗非酒精性脂肪性肝病患者肝组织PPARγ2 mRNA水平变化[J]. 实用肝脏病杂志, 2021, 24(1): 59-62. DOI: 10.3969/j.issn.1672-5069.2021.01.016.
[21]	HOU Y, MOREAU F, CHADEE K. PPARγ is an E3 ligase that induces the degradation of NFκB/p65[J]. Nat Commun, 2012, 3: 1300. DOI: 10.1038/ncomms2270.
[22]	CELINSKI K, DWORZANSKI T, FORNAL R, et al. Comparison of anti-inflammatory properties of peroxisome proliferator-activated receptor gamma agonists rosiglitazone and troglitazone in prophylactic treatment of experimental colitis[J]. J Physiol Pharmacol, 2013, 64(5): 587-595.
[23]	CHEN ZY. Effect of TFHL on the expressions of PPARs in the livers of rats with nonalcoholic steatohepatitis[J]. China J Tradit Chin Med Pharma, 2012, 27(1): 78-81. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201201024.htm 陈芝芸. 山楂叶总黄酮对非酒精性脂肪性肝炎大鼠肝脏PPARs表达的影响[J]. 中华中医药杂志, 2012, 27(1): 78-81. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201201024.htm
[24]	WANG CW. Effects of LPS on PA-induced lipid depositionin L02 cells and the role and mechanism of PPARδ, in vitro[D]. Lanzhou: Lanzhou University, 2019. 王晨薇. LPS对PA诱导的脂质沉积的肝细胞的影响及PPARδ的作用和机制的体外研究[D]. 兰州: 兰州大学, 2019.
[25]	HUANG W, PAN J, FU H. Peroxidase body growth activated receptor delta (PPAR delta) regulate glucolipid metabolism inhibiting fatty deposits of liver cells and liver fibrosis in mice[J]. Chin J Cell Mol Immunol, 2020, 36(11): 996-1001. DOI: 10.13423/j.cnki.cjcmi.009098. 黄伟, 潘瑾, 付慧. 过氧化物酶体增殖物激活受体δ(PPARδ)调节糖脂代谢抑制小鼠肝细胞脂肪沉积和肝纤维化[J]. 细胞与分子免疫学杂志, 2020, 36(11): 996-1001. DOI: 10.13423/j.cnki.cjcmi.009098.
[26]	SHI QY. Expression of FXR and PPAR α receptor and their effects on bile acid level in rats with intrahepatic cholestasis of pregnancy[P]. 2012-01-01. 时青云. FXR和PPARα受体的表达及其对妊娠肝内胆汁淤积大鼠胆汁酸水平的影响[P]. 2012-01-01.
[27]	WANG C, PENG F, ZHAONG B, et al. Metabolomic analysis reveals the therapeutic effects of MBT1805, a novel pan- peroxisome proliferator-activated receptor agonist, on α-naphthylisothiocyanate-induced cholestasis in mice[J]. Front Pharmacol, 2021, 12: 732478. DOI: 10.3389/fphar.2021.732478.
[28]	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. DOI: 10.1111/bph.13928.
[29]	PU SY, REN CY. Role of nuclear receptor FXR in hepatic stellate cells and hepatic fibrosis[J]. Progr Physiolog Sci, 2022, 53(1): 19-23. DOI: 10.3969/j.issn.0559-7765.2022.01.005. 蒲诗云, 任常谕. 核受体FXR在肝星状细胞及肝纤维化中的作用[J]. 生理科学进展, 2022, 53(1): 19-23. DOI: 10.3969/j.issn.0559-7765.2022.01.005.
[30]	GUO YT, ZHAO JM, SONG L. Rosiglitazone depressed activation of rat hepatic stellate cells in vitro[J]. Basic Clin Med, 2008, 28(11): 1129-1133. DOI: 10.3969/j.issn.1001-6325.2008.11.003. 郭晏同, 赵景明, 宋磊. 罗格列酮抑制体外大鼠肝星状细胞活化[J]. 基础医学与临床, 2008, 28(11): 1129-1133. DOI: 10.3969/j.issn.1001-6325.2008.11.003.
[31]	TAO L, WU L, ZHANG W, et al. Peroxisome proliferator-activated receptor γ inhibits hepatic stellate cell activation regulated by miR-942 in chronic hepatitis B liver fibrosis[J]. Life Sci, 2020, 253: 117572. DOI: 10.1016/j.lfs.2020.117572.
[32]	LIU H, WANG M, JIN Z, et al. FNDC5 induces M2 macrophage polarization and promotes hepatocellular carcinoma cell growth by affecting the PPARγ/NF-κB/NLRP3 pathway[J]. Biochem Biophys Res Commun, 2021, 582: 77-85. DOI: 10.1016/j.bbrc.2021.10.041.
[33]	HELLEMANS K, MICHALIK L, DITTIE A, et al. Peroxisome proliferator-activated receptor-beta signaling contributes to enhanced proliferation of hepatic stellate cells[J]. Gastroenterology, 2003, 124(1): 184-201. DOI: 10.1053/gast.2003.50015.
[34]	XIN X, YAN HZ, LI WQ, et al. Studies on PPAR α and γ participating in progression of liver fibrosis by regulating ACSL1[J]. J Clin Hepatol, 2014, 30(8): 833-835. DOI: 10.3969/j.issn.1001-5256.2014.07.034. 辛萱, 颜红柱, 李维卿, 等. 过氧化物酶体增殖物激活受体α、γ调控长链酰基辅酶A合成酶1对肝纤维化进程的影响[J]. 临床肝胆病杂志, 2014, 30(8): 833-835. DOI: 10.3969/j.issn.1001-5256.2014.07.034.
[35]	XIE GQ, LIAO GQ, MAN XB. Expression of PPARα mRNA in liver of primary hepatocellular carcinomas[J]. Chin J Clin Gastroenterol, 2009, 21(2): 97-99. DOI: 10.3870/j.issn.1005-541X.2009.02.012. 解国清, 廖国清, 满晓波. 肝细胞癌组织中PPARα mRNA的表达规律及其意义[J]. 临床消化病杂志, 2009, 21(2): 97-99. DOI: 10.3870/j.issn.1005-541X.2009.02.012.
[36]	WU CH. Effect of PPAR-α agonist pirinic acid on oxidative stress in liver tissues adjacent to hepatocellular carcinoma after TAE[D]. Dali: Dali University, 2020. 吴春华. PPAR-α激动剂匹立尼酸对肝癌TAE后癌旁肝组织氧化应激的作用[D]. 大理: 大理大学, 2020.
[37]	FAN XY, DU W, LI ZL. The effect of pirinixic acid on the expressions of PPAR-α, NF-κb and MMP-9 in paracancerous liver tissues after transarterial embolization of liver cancer[J]. J Intervent Radiol, 2020, 29(11): 1110-1115. DOI: 10.3969/j.issn.1008-794X.2020.11.011. 范馨予, 杜伟, 李正亮. 匹立尼酸对肝癌TAE术后癌旁肝组织过氧化物酶体增殖物激活受体-α、核因子-κB和基质金属蛋白酶-9表达的影响[J]. 介入放射学杂志, 2020, 29(11): 1110-1115. DOI: 10.3969/j.issn.1008-794X.2020.11.011.
[38]	DING M, ZHANG S, GUO Y, et al. Tumor microenvironment acidity triggers lipid accumulation in liver cancer via SCD1 activation[J]. Mol Cancer Res, 2022, 20(5): 810-822. DOI: 10.1158/1541-7786.MCR-21-0699.
[39]	DAI XM, LI LP, HUANG QL. Studies on the expression of Peroxisome Proliferator-activated Receptor γ(PPAR-γ) in human hepatocellula carcinoma between HBV-Related and HCV-Related infections[J]. J Med Sci Cent South China, 2012, 40(3): 253-256. DOI: 10.3969/j.issn.2095-1116.2012.03.009. 戴小明, 李彬鹏, 黄秋林. 过氧化物酶体增殖物激活受体γ在HBV、HCV感染的肝细胞癌组织中表达的研究[J]. 中南医学科学杂志, 2012, 40(3): 253-256. DOI: 10.3969/j.issn.2095-1116.2012.03.009.
[40]	LI X, ZHAO Q, QI J, et al. lncRNA Ftx promotes aerobic glycolysis and tumor progression through the PPARγ pathway in hepatocellular carcinoma[J]. Int J Oncol, 2018, 53(2): 551-566. DOI: 10.3892/ijo.2018.4418.
[41]	VACCA M, D'AMORE S, GRAZIANO G, et al. Clustering nuclear receptors in liver regeneration identifies candidate modulators of hepatocyte proliferation and hepatocarcinoma[J]. PLoS One, 2014, 9(8): e104449. DOI: 10.1371/journal.pone.0104449.
[42]	HAN W, WANG N, KONG R, et al. Ligand-activated PPARδ expression promotes hepatocellular carcinoma progression by regulating the PI3K-AKT signaling pathway[J]. J Transl Med, 2022, 20(1): 86. DOI: 10.1186/s12967-022-03288-9.
[43]	SHEN B, LI A, WAN YY, et al. Lack of PPARβ/δ-inactivated SGK-1 is implicated in liver carcinogenesis[J]. Biomed Res Int, 2020, 2020: 9563851. DOI: 10.1155/2020/9563851.
[44]	XU W, CHEN Z, LIU G, et al. Identification of a potential PPAR-related multigene signature predicting prognosis of patients with hepatocellular carcinoma[J]. PPAR Res, 2021, 2021: 6642939. DOI: 10.1155/2021/6642939.
[45]	ZHANG Z, YAO T, ZHAO N, et al. Disruption of peroxisome proliferator- activated receptor α in hepatocytes protects against acetaminophen-induced liver injury by activating the IL-6/STAT3 pathway[J]. Int J Biol Sci, 2022, 18(6): 2317-2328. DOI: 10.7150/ijbs.69609.
[46]	FAN S, HUANG X, WANG S, et al. Combinatorial usage of fungal polysaccharides from Cordyceps sinensis and Ganoderma atrum ameliorate drug-induced liver injury in mice[J]. Food Chem Toxicol, 2018, 119: 66-72. DOI: 10.1016/j.fct.2018.05.027.
[47]	LIU K, CHEN X, REN Y, et al. 3, 3', 5-triiodo-l-thyronine inhibits drug-induced liver injury through activation of PPARα as revealed by network pharmacology and biological experimental verification[J]. Toxicol Appl Pharmacol, 2022, 448: 116098. DOI: 10.1016/j.taap.2022.116098.
[48]	JI J, LI S, JIANG Z, et al. Activating PPARβ/δ protects against endoplasmic reticulum stress-induced astrocytic apoptosis via UCP2-dependent mitophagy in depressive model[J]. Int J Mol Sci, 2022, 23(18): 0822. DOI: 10.3390/ijms231810822.
[49]	FAN S, GAO Y, QU A, et al. YAP-TEAD mediates PPAR α-induced hepatomegaly and liver regeneration in mice[J]. Hepatology, 2022, 75(1): 74-88. DOI: 10.1002/hep.32105.
[50]	XIE G, YIN S, ZHANG Z, et al. Hepatocyte peroxisome proliferator-activated receptor α enhances liver regeneration after partial hepatectomy in mice[J]. Am J Pathol, 2019, 189(2): 272-282. DOI: 10.1016/j.ajpath.2018.10.009.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(1)

Get Citation

PDF

XML

Article Metrics

Article views (1248) PDF downloads(390)

Role and potential significance of peroxisome proliferator-activated receptors in liver diseases

DOI: 10.3969/j.issn.1001-5256.2023.07.034

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content