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肝线粒体功能障碍在非酒精性脂肪性肝病发病中的作用机制

杨冰清 尹静亚 王琦

引用本文:
Citation:

肝线粒体功能障碍在非酒精性脂肪性肝病发病中的作用机制

DOI: 10.12449/JCH240124
基金项目: 

国家自然科学基金面上项目 (82170591)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:杨冰清负责参考文献查阅及撰写论文;尹静亚参与论文修改;王琦负责综述构架制订,论文审校及最后定稿。
详细信息
    通信作者:

    王琦, wangqidl04@ccmu.edu.cn (ORCID: 0000-0002-0269-1568)

The mechanism of action of mitochondrial dysfunction in the development of non-alcoholic fatty liver disease

Research funding: 

National Natural Science Foundation of China (82170591)

More Information
  • 摘要: 非酒精性脂肪性肝病(NAFLD)逐渐成为影响人类肝脏健康的主要原因,其发生发展涉及多方面因素。线粒体作为细胞的“能量工厂”,对维持机体正常生理功能起着重要作用。研究表明,肝线粒体功能障碍促进NAFLD的发生发展。本文简要介绍了肝线粒体的基本特征和生理功能研究的新进展,综述了近年来线粒体功能障碍与肥胖、单纯性脂肪肝和非酒精性脂肪性肝炎关系研究方面的新成果,旨在为靶向线粒体治疗NAFLD提供研究思路。

     

  • [1] TARGHER G, COREY KE, BYRNE CD, et al. The complex link between NAFLD and type 2 diabetes mellitus-mechanisms and treatments[J]. Nat Rev Gastroenterol Hepatol, 2021, 18( 9): 599- 612. DOI: 10.1038/s41575-021-00448-y.
    [2] PAFILI K, RODEN M. Nonalcoholic fatty liver disease(NAFLD) from pathogenesis to treatment concepts in humans[J]. Mol Metab, 2021, 50: 101122. DOI: 10.1016/j.molmet.2020.101122.
    [3] RIAZI K, AZHARI H, CHARETTE JH, et al. The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2022, 7( 9): 851- 861. DOI: 10.1016/S2468-1253(22)00165-0.
    [4] NOUREDDIN M, SANYAL AJ. Pathogenesis of NASH: The impact of multiple pathways[J]. Curr Hepatol Rep, 2018, 17( 4): 350- 360. DOI: 10.1007/s11901-018-0425-7.
    [5] MANSOURI A, GATTOLLIAT CH, ASSELAH T. Mitochondrial dysfunction and signaling in chronic liver diseases[J]. Gastroenterology, 2018, 155( 3): 629- 647. DOI: 10.1053/j.gastro.2018.06.083.
    [6] CIAULA AD, PASSARELLA S, SHANMUGAM H, et al. Nonalcoholic fatty liver disease(NAFLD). Mitochondria as players and targets of therapies?[J]. Int J Mol Sci, 2021, 22( 10): 5375. DOI: 10.3390/ijms22105375.
    [7] XIAO WC, AN W. Role of mitochondrial injury in the development and progression of nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2021, 37( 7): 1515- 1521. DOI: 10.3969/j.issn.1001-5256.2021.07.005.

    肖卫纯, 安威. 线粒体损伤在非酒精性脂肪性肝病发生发展中的作用[J]. 临床肝胆病杂志, 2021, 37( 7): 1515- 1521. DOI: 10.3969/j.issn.1001-5256.2021.07.005.
    [8] TSVETKOV P, COY S, PETROVA B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins[J]. Science, 2022, 375( 6586): 1254- 1261. DOI: 10.1126/science.abf0529.
    [9] NI HM, WILLIAMS JA, DING WX. Mitochondrial dynamics and mitochondrial quality control[J]. Redox Biol, 2015, 4: 6- 13. DOI: 10.1016/j.redox.2014.11.006.
    [10] YOULE RJ, van DER BLIEK AM. Mitochondrial fission, fusion, and stress[J]. Science, 2012, 337( 6098): 1062- 1065. DOI: 10.1126/science.1219855.
    [11] CHOWANADISAI W, BAUERLY KA, TCHAPARIAN E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression[J]. J Biol Chem, 2010, 285( 1): 142- 152. DOI: 10.1074/jbc.M109.030130.
    [12] KOLIAKI C, RODEN M. Alterations of mitochondrial function and insulin sensitivity in human obesity and diabetes mellitus[J]. Annu Rev Nutr, 2016, 36: 337- 367. DOI: 10.1146/annurev-nutr-071715-050656.
    [13] XIAN HX, LIOU YC. Functions of outer mitochondrial membrane proteins: Mediating the crosstalk between mitochondrial dynamics and mitophagy[J]. Cell Death Differ, 2021, 28( 3): 827- 842. DOI: 10.1038/s41418-020-00657-z.
    [14] KOLIAKI C, SZENDROEDI J, KAUL K, et al. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis[J]. Cell Metab, 2015, 21( 5): 739- 746. DOI: 10.1016/j.cmet.2015.04.004.
    [15] POUSSIN C, IBBERSON M, HALL D, et al. Oxidative phosphorylation flexibility in the liver of mice resistant to high-fat diet-induced hepatic steatosis[J]. Diabetes, 2011, 60( 9): 2216- 2224. DOI: 10.2337/db11-0338.
    [16] PETERSEN KF, BEFROY DE, DUFOUR S, et al. Assessment of hepatic mitochondrial oxidation and pyruvate cycling in NAFLD by(13)C magnetic resonance spectroscopy[J]. Cell Metab, 2016, 24( 1): 167- 171. DOI: 10.1016/j.cmet.2016.06.005.
    [17] SUNNY NE, PARKS EJ, BROWNING JD, et al. Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease[J]. Cell Metab, 2011, 14( 6): 804- 810. DOI: 10.1016/j.cmet.2011.11.004.
    [18] PEDERSEN JS, RYGG MO, CHRØIS K, et al. Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration[J]. Nat Commun, 2022, 13( 1): 2931. DOI: 10.1038/s41467-022-30629-5.
    [19] SATAPATI S, KUCEJOVA B, DUARTE JAG, et al. Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver[J]. J Clin Invest, 2016, 126( 4): 1605. DOI: 10.1172/JCI86695.
    [20] SHAMI GJ, CHENG D, VERHAEGH P, et al. Three-dimensional ultrastructure of giant mitochondria in human non-alcoholic fatty liver disease[J]. Sci Rep, 2021, 11( 1): 3319. DOI: 10.1038/s41598-021-82884-z.
    [21] XU ZX, LUO SZ, XU MY. Mechanism of mitochondrial dysfunction in the development of nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36( 10): 2353- 2355. DOI: 10.3969/j.issn.1001-5256.2020.10.042.

    徐梓馨, 罗声政, 徐铭益. 线粒体功能异常在非酒精性脂肪性肝病发生中的机制[J]. 临床肝胆病杂志, 2020, 36( 10): 2353- 2355. DOI: 10.3969/j.issn.1001-5256.2020.10.042.
    [22] LI YF, XU JY, LU YT, et al. DRAK2 aggravates nonalcoholic fatty liver disease progression through SRSF6-associated RNA alternative splicing[J]. Cell Metab, 2021, 33( 10): 2004- 2020. DOI: 10.1016/j.cmet.2021.09.008.
    [23] CHAVIN KD, YANG S, LIN HZ, et al. Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion[J]. J Biol Chem, 1999, 274( 9): 5692- 5700. DOI: 10.1074/jbc.274.9.5692.
    [24] CORTEZ-PINTO H, CHATHAM J, CHACKO VP, et al. Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: A pilot study[J]. JAMA, 1999, 282( 17): 1659- 1664. DOI: 10.1001/jama.282.17.1659.
    [25] MORRIS EM, RECTOR RS, THYFAULT JP, et al. Mitochondria and redox signaling in steatohepatitis[J]. Antioxid Redox Signal, 2011, 15( 2): 485- 504. DOI: 10.1089/ars.2010.3795.
    [26] BEGRICHE K, IGOUDJIL A, PESSAYRE D, et al. Mitochondrial dysfunction in NASH: Causes, consequences and possible means to prevent it[J]. Mitochondrion, 2006, 6( 1): 1- 28. DOI: 10.1016/j.mito.2005.10.004.
    [27] XU JS, CHEN SY, WANG W, et al. Hepatic CDP-diacylglycerol synthase 2 deficiency causes mitochondrial dysfunction and promotes rapid progression of NASH and fibrosis[J]. Sci Bull, 2022, 67( 3): 299- 314. DOI: 10.1016/j.scib.2021.10.014.
    [28] MIYAO M, KAWAI C, KOTANI H, et al. Mitochondrial fission in hepatocytes as a potential therapeutic target for nonalcoholic steatohepatitis[J]. Hepatol Res, 2022, 52( 12): 1020- 1033. DOI: 10.1111/hepr.13832.
    [29] MONTEIRO JP, OLIVEIRA PJ, JURADO AS. Mitochondrial membrane lipid remodeling in pathophysiology: A new target for diet and therapeutic interventions[J]. Prog Lipid Res, 2013, 52( 4): 513- 528. DOI: 10.1016/j.plipres.2013.06.002.
    [30] MAGKOS F, SU X, BRADLEY D, et al. Intrahepatic diacylglycerol content is associated with hepatic insulin resistance in obese subjects[J]. Gastroenterology, 2012, 142( 7): 1444- 1446. DOI: 10.1053/j.gastro.2012.03.003.
    [31] APOSTOLOPOULOU M, GORDILLO R, KOLIAKI C, et al. Specific hepatic sphingolipids relate to insulin resistance, oxidative stress, and inflammation in nonalcoholic steatohepatitis[J]. Diabetes Care, 2018, 41( 6): 1235- 1243. DOI: 10.2337/dc17-1318.
    [32] OOI GJ, MEIKLE PJ, HUYNH K, et al. Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis[J]. J Hepatol, 2021, 75( 3): 524- 535. DOI: 10.1016/j.jhep.2021.04.013.
    [33] GAO RX, LI Y, XU ZM, et al. Mitochondrial pyruvate carrier 1 regulates fatty acid synthase lactylation and mediates treatment of nonalcoholic fatty liver disease[J]. Hepatology, 2023, 78( 6): 1800- 1815. DOI: 10.1097/HEP.0000000000000279.
    [34] LI Y, XIU WJ, XU JW, et al. Increased CHCHD2 expression promotes liver fibrosis in nonalcoholic steatohepatitis via Notch/osteopontin signaling[J]. JCI Insight, 2022, 7( 23): e162402. DOI: 10.1172/jci.insight.162402.
    [35] HE YH, ZHU MX, LIU YY, et al. Research progress of Curcumin and Resveratrol in the treatment of non-alcoholic fatty liver disease[J]. Chin Med Herald, 2023, 20( 1): 57- 60. DOI: 10.20047/j.issn1673-7210.2023.01.12.

    贺玉慧, 朱铭星, 刘跃洋, 等. 姜黄素与白藜芦醇治疗非酒精性脂肪性肝病的机制研究进展[J]. 中国医药导报, 2023, 20( 1): 57- 60. DOI: 10.20047/j.issn1673-7210.2023.01.12.
    [36] GEORGIEV A, GRANATA C, RODEN M. The role of mitochondria in the pathophysiology and treatment of common metabolic diseases in humans[J]. Am J Physiol Cell Physiol, 2022, 322( 6): C1248- C1259. DOI: 10.1152/ajpcell.00035.2022.
    [37] GRANATA C, JAMNICK NA, BISHOP DJ. Training-induced changes in mitochondrial content and respiratory function in human skeletal muscle[J]. Sports Med, 2018, 48( 8): 1809- 1828. DOI: 10.1007/s40279-018-0936-y.
    [38] THIETART S, RAUTOU PE. Extracellular vesicles as biomarkers in liver diseases: A clinician’s point of view[J]. J Hepatol, 2020, 73( 6): 1507- 1525. DOI: 10.1016/j.jhep.2020.07.014.
    [39] AMIR DACHE Z AL, OTANDAULT A, TANOS R, et al. Blood contains circulating cell-free respiratory competent mitochondria[J]. FASEB J, 2020, 34( 3): 3616- 3630. DOI: 10.1096/fj.201901917RR.
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出版历程
  • 收稿日期:  2023-04-17
  • 录用日期:  2023-06-19
  • 出版日期:  2024-01-23
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