中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 5
May  2023
Turn off MathJax
Article Contents

Association between bile acids and nonalcoholic fatty liver disease

DOI: 10.3969/j.issn.1001-5256.2023.05.026
Research funding:

National Natural Science Foundation of China (81970528)

More Information
  • Corresponding author: LU Lungen, lungenlu1965@163.com (ORCID: 0000-0003-4301-9513)
  • Received Date: 2022-09-19
  • Accepted Date: 2022-11-21
  • Published Date: 2023-05-20
  • With the rapid increase in the prevalence rate of nonalcoholic fatty liver disease (NAFLD), new treatment methods are needed to prevent disease progression to liver fibrosis, liver cirrhosis, and liver cancer. Although great efforts have been made to clarify the pathological mechanisms of NAFLD disease progression, there are still no effective treatment methods at present. Bile acids (BAs) regulate systemic metabolism by activating nuclear receptors and G protein-coupled receptors and have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis is associated with the severity of NAFLD. This article summarizes the important ligands in BA metabolism and their role in the progression of NAFLD, in order to provide a basis for the treatment of NAFLD by targeting BA messengers.

     

  • loading
  • [1]
    SAYINER M, KOENIG A, HENRY L, et al. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in the United States and the rest of the world[J]. Clin Liver Dis, 2016, 20(2): 205-214. DOI: 10.1016/j.cld.2015.10.001.
    [2]
    RINELLA ME. Nonalcoholic fatty liver disease: a systematic review[J]. Jama, 2015, 313(22): 2263-2273. DOI: 10.1001/jama.2015.5370.
    [3]
    ARAB JP, KARPEN SJ, DAWSON PA, et al. Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives[J]. Hepatology, 2017, 65(1): 350-362. DOI: 10.1002/hep.28709.
    [4]
    TANAKA N, MATSUBARA T, KRAUSZ KW, et al. Disruption of phospholipid and bile acid homeostasis in mice with nonalcoholic steatohepatitis[J]. Hepatology, 2012, 56(1): 118-129. DOI: 10.1002/hep.25630.
    [5]
    FERSLEW BC, XIE G, JOHNSTON CK, et al. Altered bile acid metabolome in patients with nonalcoholic steatohepatitis[J]. Dig Dis Sci, 2015, 60(11): 3318-3328. DOI: 10.1007/s10620-015-3776-8.
    [6]
    SUGA T, YAMAGUCHI H, OGURA J, et al. Altered bile acid composition and disposition in a mouse model of non-alcoholic steatohepatitis[J]. Toxicol Appl Pharmacol, 2019, 379: 114664. DOI: 10.1016/j.taap.2019.114664.
    [7]
    NIMER N, CHOUCAIR I, WANG Z, et al. Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease progression[J]. Metabolism, 2021, 116: 154457. DOI: 10.1016/j.metabol.2020.154457.
    [8]
    BECHMANN LP, KOCABAYOGLU P, SOWA JP, et al. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis[J]. Hepatology, 2013, 57(4): 1394-1406. DOI: 10.1002/hep.26225.
    [9]
    WEI S, MA X, ZHAO Y. Mechanism of hydrophobic bile acid-induced hepatocyte injury and drug discovery[J]. Front Pharmacol, 2020, 11: 1084. DOI: 10.3389/fphar.2020.01084.
    [10]
    KATAFUCHI T, MAKISHIMA M. Molecular basis of bile acid-FXR-FGF15/19 signaling axis[J]. Int J Mol Sci, 2022, 23(11): 6046. DOI: 10.3390/ijms23116046.
    [11]
    MARTINOT E, SōDES L, BAPTISSART M, et al. Bile acids and their receptors[J]. Mol Aspects Med, 2017, 56: 2-9. DOI: 10.1016/j.mam.2017.01.006.
    [12]
    WAN YY, SHENG L. Regulation of bile acid receptor activity[J]. Liver Res, 2018, 2(4): 180-185. DOI: 10.1016/j.livres.2018.09.008.
    [13]
    XIANG J, ZHANG Z, XIE H, et al. Effect of different bile acids on the intestine through enterohepatic circulation based on FXR[J]. Gut Microbes, 2021, 13(1): 1949095. DOI: 10.1080/19490976.2021.1949095.
    [14]
    KEITEL V, CUPISTI K, ULLMER C, et al. The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders[J]. Hepatology, 2009, 50(3): 861-870. DOI: 10.1002/hep.23032.
    [15]
    MERLEN G, KAHALE N, URSIC-BEDOYA J, et al. TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function[J]. Gut, 2020, 69(1): 146-157. DOI: 10.1136/gutjnl-2018-316975.
    [16]
    PERINO A, SCHOONJANS K. Metabolic messengers: bile acids[J]. Nat Metab, 2022, 4(4): 416-423. DOI: 10.1038/s42255-022-00559-z.
    [17]
    CARIOU B, van HARMELEN K, DURAN-SANDOVAL D, et al. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice[J]. J Biol Chem, 2006, 281(16): 11039-11049. DOI: 10.1074/jbc.M510258200.
    [18]
    CARR RM, REID AE. FXR agonists as therapeutic agents for non-alcoholic fatty liver disease[J]. Curr Atheroscler Rep, 2015, 17(4): 500. DOI: 10.1007/s11883-015-0500-2.
    [19]
    JAHN D, RAU M, HERMANNS HM, et al. Mechanisms of enterohepatic fibroblast growth factor 15/19 signaling in health and disease[J]. Cytokine Growth Factor Rev, 2015, 26(6): 625-635. DOI: 10.1016/j.cytogfr.2015.07.016.
    [20]
    BAGGIO LL, DRUCKER DJ. Biology of incretins: GLP-1 and GIP[J]. Gastroenterology, 2007, 132(6): 2131-2157. DOI: 10.1053/j.gastro.2007.03.054.
    [21]
    KUMAR DP, ASGHARPOUR A, MIRSHAHI F, et al. Activation of transmembrane bile acid receptor TGR5 modulates pancreatic islet α cells to promote glucose homeostasis[J]. J Biol Chem, 2016, 291(13): 6626-6640. DOI: 10.1074/jbc.M115.699504.
    [22]
    SINAL CJ, TOHKIN M, MIYATA M, et al. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis[J]. Cell, 2000, 102(6): 731-744. DOI: 10.1016/s0092-8674(00)00062-3.
    [23]
    WATANABE M, HOUTEN SM, WANG L, et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c[J]. J Clin Invest, 2004, 113(10): 1408-1418. DOI: 10.1172/JCI21025.
    [24]
    FUCHS CD, TRAUSSNIGG SA, TRAUNER M. Nuclear receptor modulation for the treatment of nonalcoholic fatty liver disease[J]. Semin Liver Dis, 2016, 36(1): 69-86. DOI: 10.1055/s-0036-1571296.
    [25]
    CLIFFORD BL, SEDGEMAN LR, WILLIAMS KJ, et al. FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption[J]. Cell Metab, 2021, 33(8): 1671-1684. e4. DOI: 10.1016/j.cmet.2021.06.012.
    [26]
    WATANABE M, HOUTEN SM, MATAKI C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation[J]. Nature, 2006, 439(7075): 484-489. DOI: 10.1038/nature04330.
    [27]
    SELWYN FP, CSANAKY IL, ZHANG Y, et al. Importance of large intestine in regulating bile acids and glucagon-like peptide-1 in germ-free mice[J]. Drug Metab Dispos, 2015, 43(10): 1544-1556. DOI: 10.1124/dmd.115.065276.
    [28]
    PERINO A, DEMAGNY H, VELAZQUEZ-VILLEGAS L, et al. Molecular physiology of bile acid signaling in health, disease, and aging[J]. Physiol Rev, 2021, 101(2): 683-731. DOI: 10.1152/physrev.00049.2019.
    [29]
    FUJISAKA S, USSAR S, CLISH C, et al. Antibiotic effects on gut microbiota and metabolism are host dependent[J]. J Clin Invest, 2016, 126(12): 4430-4443. DOI: 10.1172/JCI86674.
    [30]
    SAYIN SI, WAHLSTRÖM A, FELIN J, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist[J]. Cell Metab, 2013, 17(2): 225-235. DOI: 10.1016/j.cmet.2013.01.003.
    [31]
    LIU Y, CHEN K, LI F, et al. Probiotic lactobacillus rhamnosus GG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice[J]. Hepatology, 2020, 71(6): 2050-2066. DOI: 10.1002/hep.30975.
    [32]
    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.
    [33]
    LONG SL, GAHAN C, JOYCE SA. Interactions between gut bacteria and bile in health and disease[J]. Mol Aspects Med, 2017, 56: 54-65. DOI: 10.1016/j.mam.2017.06.002.
    [34]
    ISLAM KB, FUKIYA S, HAGIO M, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats[J]. Gastroenterology, 2011, 141(5): 1773-1781. DOI: 10.1053/j.gastro.2011.07.046.
    [35]
    FRIEDMAN ES, LI Y, SHEN TD, et al. FXR-dependent modulation of the human small intestinal microbiome by the bile acid derivative obeticholic acid[J]. Gastroenterology, 2018, 155(6): 1741-1752. e5. DOI: 10.1053/j.gastro.2018.08.022.
    [36]
    JIAO N, BAKER SS, CHAPA-RODRIGUEZ A, et al. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD[J]. Gut, 2018, 67(10): 1881-1891. DOI: 10.1136/gutjnl-2017-314307.
    [37]
    JANSSEN A, HOUBEN T, KATIRAEI S, et al. Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids[J]. J Lipid Res, 2017, 58(7): 1399-1416. DOI: 10.1194/jlr.M075713.
    [38]
    ZHANG L, XIE C, NICHOLS RG, et al. Farnesoid X receptor signaling shapes the gut microbiota and controls hepatic lipid metabolism[J]. mSystems, 2016, 1(5): e00070. DOI: 10.1128/mSystems.00070-16.
    [39]
    JIANG C, XIE C, LV Y, et al. Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction[J]. Nat Commun, 2015, 6: 10166. DOI: 10.1038/ncomms10166.
    [40]
    LOOMBA R, SEGURITAN V, LI W, et al. Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease[J]. Cell Metab, 2019, 30(3): 607. DOI: 10.1016/j.cmet.2019.08.002.
    [41]
    FUCHS CD, TRAUNER M. Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology[J]. Nat Rev Gastroenterol Hepatol, 2022, 19(7): 432-450. DOI: 10.1038/s41575-021-00566-7.
    [42]
    TRAUNER M, NEVENS F, SHIFFMAN ML, et al. Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study[J]. Lancet Gastroenterol Hepatol, 2019, 4(6): 445-453. DOI: 10.1016/S2468-1253(19)30094-9.
    [43]
    YOUNOSSI ZM, RATZIU V, LOOMBA R, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial[J]. Lancet, 2019, 394(10215): 2184-2196. DOI: 10.1016/S0140-6736(19)33041-7.
    [44]
    KOHLI R, MYRONOVYCH A, TAN BK, et al. Bile acid signaling: mechanism for bariatric surgery, cure for NASH?[J]. Dig Dis, 2015, 33(3): 440-446. DOI: 10.1159/000371699.
    [45]
    TREMAROLI V, KARLSSON F, WERLING M, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation[J]. Cell Metab, 2015, 22(2): 228-238. DOI: 10.1016/j.cmet.2015.07.009.
  • 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

    Article Metrics

    Article views (400) PDF downloads(145) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return