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胆汁酸与非酒精性脂肪性肝病的关系

王俊俊 蔡晓波 陆伦根

引用本文:
Citation:

胆汁酸与非酒精性脂肪性肝病的关系

DOI: 10.3969/j.issn.1001-5256.2023.05.026
基金项目: 

国家自然科学基金 (81970528)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:王俊俊负责查阅文献,撰写文章;蔡晓波负责文献审核,修改文章;陆伦根负责拟定写作思路,指导撰写文章并最终定稿。
详细信息
    通信作者:

    陆伦根, lungenlu1965@163.com (ORCID: 0000-0003-4301-9513)

Association between bile acids and nonalcoholic fatty liver disease

Research funding: 

National Natural Science Foundation of China (81970528)

More Information
  • 摘要: 非酒精性脂肪性肝病(NAFLD)患病率的迅速增加亟需新的治疗方法来预防疾病进展为肝纤维化、肝硬化及肝癌。尽管已经为阐明NAFLD疾病进展的病理机制做出了不懈努力,但目前尚无有效的治疗方法。胆汁酸(BA)通过激活核受体和G蛋白偶联受体调控全身代谢,已被确定为参与脂质、葡萄糖和能量代谢的重要信号分子。BA稳态的失调与NAFLD疾病的严重程度有关。本文总结了BA代谢中的重要配体和其在NAFLD进展中的作用,以期为靶向BA信使治疗NAFLD提供依据。

     

  • [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.
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  • 收稿日期:  2022-09-19
  • 录用日期:  2022-11-21
  • 出版日期:  2023-05-20
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