中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Menu
Volume 40 Issue 10
Oct.  2024
Turn off MathJax
Article Contents
Abstract
References
Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(10): 1954-1958

Research advances in the pathogenesis of metabolic associated fatty liver disease

DOI: 10.12449/JCH241005

  • Department of Gastroenterology，China-Japan Friendship Hospital，Beijing 100029，China

Research funding:

Joint Fund Project of Biomedical Translational Engineering Research Center of Beijing University of Chemical Technology and China-Japan Friendship Hospital (XK2022-07)

More Information
  • Corresponding author: YAO Shukun， shukunyao@126.com （ORCID： 0000-0002-8512-2589）
  • Received Date: 2024-08-23
  • Accepted Date: 2024-09-10
  • Published Date: 2024-10-25
    Abstract
  • Metabolic associated fatty liver disease （MAFLD） is currently the most common liver disease around the world. MAFLD may easily progress to the adverse outcomes such as hepatitis， liver fibrosis， and liver cirrhosis， and it is often accompanied by comorbidities such as diabetes， hypertension， hyperlipidemia， hyperuricemia， and cardiovascular and cerebrovascular diseases. Etiological treatment is the cornerstone of MAFLD treatment， and due to the complexity and adverse outcome of MAFLD， it is of great significance to explore the pathogenesis of MAFLD and develop effective prevention and treatment regimens and drugs. This article reviews the pathogenesis of MAFLD from the aspects of genetic factors， improper diet and oxidative stress， spleen-stomach damp-heat and insulin resistance， damp-heat and pathogenic Qi， organic acid metabolism， and intestinal microecology.

     

    • FullText(HTML)
    • References(56)
  • [1]
    YOUNOSSI Z, ANSTEE QM, MARIETTI M, et al. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2018, 15( 1): 11- 20. DOI: 10.1038/nrgastro.2017.109.
    [2]
    ESLAM M, SANYAL AJ, GEORGE J, et al. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J]. Gastroenterology, 2020, 158( 7): 1999- 2014. e 1. DOI: 10.1053/j.gastro.2019.11.312.
    [3]
    DULAI PS, SINGH S, PATEL J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis[J]. Hepatology, 2017, 65( 5): 1557- 1565. DOI: 10.1002/hep.29085.
    [4]
    KUCHAY MS, CHOUDHARY NS, MISHRA SK. Pathophysiological mechanisms underlying MAFLD[J]. Diabetes Metab Syndr, 2020, 14( 6): 1875- 1887. DOI: 10.1016/j.dsx.2020.09.026.
    [5]
    ROMEO S, KOZLITINA J, XING C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease[J]. Nat Genet, 2008, 40( 12): 1461- 1465. DOI: 10.1038/ng.257.
    [6]
    SOOKOIAN S, PIROLA CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene(PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease[J]. Hepatology, 2011, 53( 6): 1883- 1894. DOI: 10.1002/hep.24283.
    [7]
    VALENTI L, AL-SERRI A, DALY AK, et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease[J]. Hepatology, 2010, 51( 4): 1209- 1217. DOI: 10.1002/hep.23622.
    [8]
    LUUKKONEN PK, ZHOU Y, NIDHINA HARIDAS PA, et al. Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD[J]. J Hepatol, 2017, 67( 1): 128- 136. DOI: 10.1016/j.jhep.2017.02.014.
    [9]
    PIROLA CJ, GARAYCOECHEA M, FLICHMAN D, et al. Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease[J]. J Lipid Res, 2019, 60( 1): 176- 185. DOI: 10.1194/jlr.P089953.
    [10]
    SU W, PENG J, LI S, et al. Liver X receptor α induces 17β-hydroxysteroid dehydrogenase-13 expression through SREBP-1c[J]. Am J Physiol Endocrinol Metab, 2017, 312( 4): E357- E367. DOI: 10.1152/ajpendo.00310.2016.
    [11]
    ABUL-HUSN NS, CHENG XP, LI AH, et al. A protein-truncating HSD17B13 variant and protection from chronic liver disease[J]. N Engl J Med, 2018, 378( 12): 1096- 1106. DOI: 10.1056/NEJMoa1712191.
    [12]
    LUUKKONEN PK, TUKIAINEN T, JUUTI A, et al. Hydroxysteroid 17-β dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease[J]. JCI Insight, 2020, 5( 5): e132158. DOI: 10.1172/jci.insight.132158.
    [13]
    ROBERTSON G, LECLERCQ I, FARRELL GC. Nonalcoholic steatosis and steatohepatitis. II. Cytochrome P-450 enzymes and oxidative stress[J]. Am J Physiol Gastrointest Liver Physiol, 2001, 281( 5): G1135- G1139. DOI: 10.1152/ajpgi.2001.281.5.G1135.
    [14]
    ROLO AP, TEODORO JS, PALMEIRA CM. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis[J]. Free Radic Biol Med, 2012, 52( 1): 59- 69. DOI: 10.1016/j.freeradbiomed.2011.10.003.
    [15]
    YESILOVA Z, YAMAN H, OKTENLI C, et al. Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic Fatty liver disease[J]. Am J Gastroenterol, 2005, 100( 4): 850- 855. DOI: 10.1111/j.1572-0241.2005.41500.x.
    [16]
    PARADIES G, PARADIES V, RUGGIERO FM, et al. Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2014, 20( 39): 14205- 14218. DOI: 10.3748/wjg.v20.i39.14205.
    [17]
    ZHOU ZK, WANG YY, JIANG YM, et al. Deep-fried oil consumption in rats impairs glycerolipid metabolism, gut histology and microbiota structure[J]. Lipds Health Dis, 2016, 15( 1): 86. DOI: 10.1186/s12944-016-0252-1.
    [18]
    XUE LJ, HAN JQ, ZHOU YC, et al. Untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease induced by high-temperature-processed feed in Sprague-Dawley rats[J]. World J Gastroenterol, 2020, 26( 46): 7299- 7311. DOI: 10.3748/wjg.v26.i46.7299.
    [19]
    RINALDO-MATTHIS A, HAEGGSTRÖM JZ. Structures and mechanisms of enzymes in the leukotriene cascade[J]. Biochimie, 2010, 92( 6): 676- 681. DOI: 10.1016/j.biochi.2010.01.010.
    [20]
    ZHANG NP, LIU XJ, XIE L, et al. Impaired mitophagy triggers NLRP3 inflammasome activation during the progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis[J]. Lab Invest, 2019, 99( 6): 749- 763. DOI: 10.1038/s41374-018-0177-6.
    [21]
    BARBIER-TORRES L, FORTNER KA, IRUZUBIETA P, et al. Silencing hepatic MCJ attenuates non-alcoholic fatty liver disease(NAFLD) by increasing mitochondrial fatty acid oxidation[J]. Nat Commun, 2020, 11( 1): 3360. DOI: 10.1038/s41467-020-16991-2.
    [22]
    LI CG, HSIEH MC, CHANG SJ. Metabolic syndrome, diabetes, and hyperuricemia[J]. Curr Opin Rheumatol, 2013, 25( 2): 210- 216. DOI: 10.1097/BOR.0b013e32835d951e.
    [23]
    FORLANI G, GIORDA C, MANTI R, et al. The burden of NAFLD and its characteristics in a nationwide population with type 2 diabetes[J]. J Diabetes Res, 2016, 2016: 2931985. DOI: 10.1155/2016/2931985.
    [24]
    SHEN Q, TAN X, WANG WZ. Autonomic nervous dysfunction caused by circadian disruption: research progress[J]. Acad J Naval Med Uni, 2024, 45( 3): 328- 332. DOI: 10.16781/j.CN31-2187/R.20230605.

    沈琦, 谭兴, 王伟忠. 昼夜节律紊乱导致自主神经功能失衡的研究进展[J]. 海军军医大学学报, 2024, 45( 3): 328- 332. DOI: 10.16781/j.CN31-2187/R.20230605.
    [25]
    ZHENG XY, GONG LL, LUO R, et al. Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults[J]. Lipds Health Dis, 2017, 16( 1): 202. DOI: 10.1186/s12944-017-0531-5.
    [26]
    LIU J, WANG C, WANG YT, et al. Hyperuricemia as an independent risk factor for metabolic dysfunction-associated fatty liver disease in nonobese patients without type 2 diabetes mellitus[J]. Am J Physiol Endocrinol Metab, 2023, 325( 1): E62- E71. DOI: 10.1152/ajpendo.00001.2023.
    [27]
    JENSEN T, NIWA K, HISATOME I, et al. Increased serum uric acid over five years is a risk factor for developing fatty liver[J]. Sci Rep, 2018, 8( 1): 11735. DOI: 10.1038/s41598-018-30267-2.
    [28]
    ZHOU YJ, WEI FF, FAN Y. High serum uric acid and risk of nonalcoholic fatty liver disease: A systematic review and meta-analysis[J]. Clin Biochem, 2016, 49( 7-8): 636- 642. DOI: 10.1016/j.clinbiochem.2015.12.010.
    [29]
    SPAHIS S, DELVIN E, BORYS JM, et al. Oxidative stress as a critical factor in nonalcoholic fatty liver disease pathogenesis[J]. Antioxid Redox Signal, 2017, 26( 10): 519- 541. DOI: 10.1089/ars.2016.6776.
    [30]
    LIU N, XU H, SUN QQ, et al. The role of oxidative stress in hyperuricemia and xanthine oxidoreductase(XOR) inhibitors[J]. Oxid Med Cell Longev, 2021, 2021: 1470380. DOI: 10.1155/2021/1470380.
    [31]
    VANDANMAGSAR B, YOUM YH, RAVUSSIN A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance[J]. Nat Med, 2011, 17( 2): 179- 188. DOI: 10.1038/nm.2279.
    [32]
    CHOE EK, KANG HY, PARK B, et al. The association between nonalcoholic fatty liver disease and CT-measured skeletal muscle mass[J]. J Clin Med, 2018, 7( 10): 310. DOI: 10.3390/jcm7100310.
    [33]
    UTZSCHNEIDER KM, KAHN SE. Review: The role of insulin resistance in nonalcoholic fatty liver disease[J]. J Clin Endocrinol Metab, 2006, 91( 12): 4753- 4761. DOI: 10.1210/jc.2006-0587.
    [34]
    ZHAI Y, XIAO Q. The common mechanisms of sarcopenia and NAFLD[J]. Biomed Res Int, 2017, 2017: 6297651. DOI: 10.1155/2017/6297651.
    [35]
    NEWGARD CB, AN J, BAIN JR, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance[J]. Cell Metab, 2009, 9( 4): 311- 326. DOI: 10.1016/j.cmet.2009.02.002.
    [36]
    WANG TJ, LARSON MG, VASAN RS, et al. Metabolite profiles and the risk of developing diabetes[J]. Nat Med, 2011, 17( 4): 448- 453. DOI: 10.1038/nm.2307.
    [37]
    GOFFREDO M, SANTORO N, TRICÒ D, et al. A branched-chain amino acid-related metabolic signature characterizes obese adolescents with non-alcoholic fatty liver disease[J]. Nutrients, 2017, 9( 7): 642. DOI: 10.3390/nu9070642.
    [38]
    MASARONE M, TROISI J, AGLITTI A, et al. Untargeted metabolomics as a diagnostic tool in NAFLD: Discrimination of steatosis, steatohepatitis and cirrhosis[J]. Metabolomics, 2021, 17( 2): 12. DOI: 10.1007/s11306-020-01756-1.
    [39]
    KOLODZIEJCZYK AA, ZHENG DP, SHIBOLET O, et al. The role of the microbiome in NAFLD and NASH[J]. EMBO Mol Med, 2019, 11( 2): e9302. DOI: 10.15252/emmm.201809302.
    [40]
    DEN BESTEN G, LANGE K, HAVINGA R, et al. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids[J]. Am J Physiol Gastrointest Liver Physiol, 2013, 305( 12): G900- G910. DOI: 10.1152/ajpgi.00265.2013.
    [41]
    SUN MM, WU W, LIU ZJ, et al. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases[J]. J Gastroenterol, 2017, 52( 1): 1- 8. DOI: 10.1007/s00535-016-1242-9.
    [42]
    KIM M, LEE HA, CHO HM, et al. Histone deacetylase inhibition attenuates hepatic steatosis in rats with experimental Cushing’s syndrome[J]. Korean J Physiol Pharmacol, 2018, 22( 1): 23- 33. DOI: 10.4196/kjpp.2018.22.1.23.
    [43]
    CHEN YM, LIU Y, ZHOU RF, et al. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults[J]. Sci Rep, 2016, 6: 19076. DOI: 10.1038/srep19076.
    [44]
    KOETH RA, WANG ZN, LEVISON BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis[J]. Nat Med, 2013, 19( 5): 576- 585. DOI: 10.1038/nm.3145.
    [45]
    ZHANG H, SUN H, LIAO H. Mechanism of inducing microglial inflammatory response in patients with depression[J]. Basic Clin Med, 2024, 44( 7): 1029- 1033. DOI: 10.16352/j.issn.1001-6325.2024.07.1029.

    张昊, 孙浩, 廖红. 诱导抑郁症患者小胶质细胞炎性反应的机制[J]. 基础医学与临床, 2024, 44( 7): 1029- 1033. DOI: 10.16352/j.issn.1001-6325.2024.07.1029.
    [46]
    WEI Y, CHANG LJ, HASHIMOTO K. Molecular mechanisms underlying the antidepressant actions of arketamine: Beyond the NMDA receptor[J]. Mol Psychiatry, 2022, 27: 559- 573. DOI: 10.1038/s41380-021-01121-1.
    [47]
    TILG H, ADOLPH TE, TRAUNER M. Gut-liver axis: Pathophysiological concepts and clinical implications[J]. Cell Metab, 2022, 34( 11): 1700- 1718. DOI: 10.1016/j.cmet.2022.09.017.
    [48]
    ZHU LX, BAKER SS, GILL C, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis(NASH) patients: A connection between endogenous alcohol and NASH[J]. Hepatology, 2013, 57( 2): 601- 609. DOI: 10.1002/hep.26093.
    [49]
    VOLYNETS V, KÜPER MA, STRAHL S, et al. Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with nonalcoholic fatty liver disease(NAFLD)[J]. Dig Dis Sci, 2012, 57( 7): 1932- 1941. DOI: 10.1007/s10620-012-2112-9.
    [50]
    YUAN J, CHEN C, CUI JH, et al. Fatty liver disease caused by high-alcohol-producing Klebsiella pneumoniae[J]. Cell Metab, 2019, 30( 4): 675- 688. e 7. DOI: 10.1016/j.cmet.2019.08.018.
    [51]
    KAKIYAMA G, PANDAK WM, GILLEVET PM, et al. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis[J]. J Hepatol, 2013, 58( 5): 949- 955. DOI: 10.1016/j.jhep.2013.01.003.
    [52]
    CHÁVEZ-TALAVERA O, TAILLEUX A, LEFEBVRE P, et al. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease[J]. Gastroenterology, 2017, 152( 7): 1679- 1694. e 3. DOI: 10.1053/j.gastro.2017.01.055.
    [53]
    RIDLON JM, KANG DJ, HYLEMON PB, et al. Bile acids and the gut microbiome[J]. Curr Opin Gastroenterol, 2014, 30( 3): 332- 338. DOI: 10.1097/MOG.0000000000000057.
    [54]
    SPENCER MD, HAMP TJ, REID RW, et al. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency[J]. Gastroenterology, 2011, 140( 3): 976- 986. DOI: 10.1053/j.gastro.2010.11.049.
    [55]
    ARON-WISNEWSKY J, CLÉMENT K. The gut microbiome, diet, and links to cardiometabolic and chronic disorders[J]. Nat Rev Nephrol, 2016, 12( 3): 169- 181. DOI: 10.1038/nrneph.2015.191.
    [56]
    TANG WH, WANG ZN, LEVISON BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk[J]. N Engl J Med, 2013, 368( 17): 1575- 1584. DOI: 10.1056/NEJMoa1109400.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    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

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索
    Get Citation
    PDF
    XML

    Article Metrics

    Article views (1123) PDF downloads(88) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[2389]YesterdayPV[5285]TodayIP[1445]TodayPV[3050]Online[129]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return