Role of Abnormal Bile Acid Metabolism in the Development of Non-alcoholic Fatty Liver Disease
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摘要: 非酒精性脂肪性肝病逐渐成为全球儿童发病率最高的慢性肝病之一,肠肝循环中扮演重要角色的胆汁酸在其发病机制中的作用日渐突出。近年来,研究发现胆汁酸是法尼醇X受体和G蛋白偶联受体5的信号分子,二者作为胆汁酸受体调控全身代谢。胆汁酸代谢失衡与NAFLD严重程度密切相关。对胆汁酸及其受体在NAFLD进展中的作用进行综述,以期为NAFLD无创诊断及治疗提供新的靶点。Abstract: Non-alcoholic fatty liver disease is emerging as one of the most prevalent chronic liver diseases in children worldwide, and bile acids, which play an important role in the enterohepatic circulation are becoming increasingly prominent in its pathogenesis. In recent years, it has been found that bile acids are[
1 ] signaling molecules for farnesol X receptor and G protein-coupled receptor 5, both of which act as bile acid receptors to regulate systemic metabolism. The imbalance of bile acid metabolism is closely related to the severity of NAFLD. This article reviews the role of bile acids and their receptors in the progression of NAFLD with the aim of providing new targets for the noninvasive diagnosis and treatment of NAFLD. -
[1] Younossi Z M,Koenig A B,Abdelatif D,et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J]. Hepatology,2016,64(1):73-84. doi: 10.1002/hep.28431 [2] Li J,Zou B,Yeo Y H,et al. Prevalence,incidence,and outcome of non-alcoholic fatty liver disease in Asia,1999-2019: A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol,2019,4(5):389-398. doi: 10.1016/S2468-1253(19)30039-1 [3] Machado M V,Cortez-Pinto H. Non-alcoholic fatty liver disease: What the clinician needs to know[J]. World J Gastroenterol,2014,20(36):12956-12980. doi: 10.3748/wjg.v20.i36.12956 [4] Chávez-Talavera O,Tailleux A,Lefebvre P,et al. Bile acid control of metabolism and inflammation in obesity,type2 diabetes,dyslipidemia,and nonalcoholic fatty liver disease[J]. Gastroenterology,2017,152(7):1679-1694. doi: 10.1053/j.gastro.2017.01.055 [5] Bechmann L P,Kocabayoglu P,Sowa J P,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. [6] Puri P,Daita K,Joyce A,et al. The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids[J]. Hepatology,2018,67(2):534-548. doi: 10.1002/hep.29359 [7] Chow M D,Lee Y H,Guo G L. The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Mol Aspects Med,2017,56(4):34-44. [8] Xue R,Su L,Lai S,et al. Bile acid receptors and the gut-liver axis in nonalcoholic fatty liver disease[J]. Cells,2021,10(11):2806. doi: 10.3390/cells10112806 [9] Yang Z X,Shen W,Sun H. Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease[J]. Hepatol Int,2010,4(4):741-748. doi: 10.1007/s12072-010-9202-6 [10] Jiao N,Baker S S,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 [11] Arab J P,Karpen S J,Dawson P A,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 [12] Sinal C J,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 [13] Manchekar M,Kapil R,Sun Z,et al. Relationship between amphipathic β Structures in the β1domain of apolipoprotein B and the properties of the secreted lipoprotein particles in McA-RH7777 cells[J]. Biochemistry,2017,56(31):4084-4094. doi: 10.1021/acs.biochem.6b01174 [14] Chiang J Y. Bile acid metabolism and signaling[J]. Compr Physiol,2013,3(3):1191-1212. [15] Deng W,Fan W,Tang T,et al. Farnesoid X receptor deficiency induces hepatic lipid and glucose metabolism disorder via regulation of pyruvate dehydrogenase kinase 4[J]. Oxid Med Cell Longev,2022,2022:3589525. [16] Herzig S,Long F,Jhala U S,et al. CREB regulates hepatic gluconeogenesisthrough the coactivator PGC-1[J]. Nature,2001,413(6852):179-183. doi: 10.1038/35093131 [17] Carino A,Cipriani S,Marchianò S,et al. Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice[J]. Sci Rep,2017,7(1):13689. doi: 10.1038/s41598-017-13102-y [18] Velazquez-Villegas L A,Perino A,Lemos V,et al. TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue[J]. Nat Commun,2018,9(1):245. doi: 10.1038/s41467-017-02068-0 [19] Thomas C,Gioiello A,Noriega L,et al. TGR5-mediated bile acid sensing controls glucose homeostasis[J]. Cell Metab,2009,10(3):167-177. doi: 10.1016/j.cmet.2009.08.001 [20] Fang S,Suh J M,Reilly S M,et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance[J]. Nat Med,2015,21(2):159-165. doi: 10.1038/nm.3760 [21] Seok S,Sun H,Kim Y C,et al. Defective FXR-SHP regulation in obesity aberrantly increases miR-802 expression,promoting insulin resistance and fatty liver[J]. Diabetes,2021,70(3):733-744. doi: 10.2337/db20-0856 [22] Ding L,Yang L,Wang Z,et al. Bile acid nuclear receptor FXR and digestive system diseases[J]. Acta Pharm Sin B,2015,5(2):135-144. doi: 10.1016/j.apsb.2015.01.004 [23] Goldspink D A,Lu V B,Billing L J,et al. Mechanistic insights into the detection of free fatty and bile acids by ileal glucagon-like peptide-1 secreting cells[J]. Mol Metab,2018,7:90-101. doi: 10.1016/j.molmet.2017.11.005 [24] Drucker D J. The biology of incretin hormones[J]. Cell Metab,2006,3(3):153-165. doi: 10.1016/j.cmet.2006.01.004 [25] Katsuma S,Hirasawa A,Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1[J]. Biochem Biophys Res Commun,2005,329(1):386-390. doi: 10.1016/j.bbrc.2005.01.139 [26] Holter M M,Chirikjian M K,Briere D A,et al. Compound 18 improves glucose tolerance in a hepatocyte TGR5-dependent manner in mice[J]. Nutrients,2020,12(7):2124. doi: 10.3390/nu12072124 [27] Lefebvre P,Cariou B,Lien F,et al. Role of bile acids and bile acid receptors in metabolic regulation[J]. Physiol Rev,2009,89(1):147-191. doi: 10.1152/physrev.00010.2008 [28] Fiorucci S,Di Giorgio C,Distrutti E. Obeticholic acid: An update of its pharmacological activities in liver disorders[J]. Handb Exp Pharmacol,2019,256:283-295. [29] Briand F,Brousseau E,Quinsat M,et al. Obeticholic acid raises LDL-cholesterol and reduces HDL-cholesterol in the diet-induced NASH (DIN) hamster model[J]. Eur J Pharmacol,2018,818:449-456. doi: 10.1016/j.ejphar.2017.11.021 [30] Yu Y,Liu Y,An W,et al. STING-mediated inflammation in Kupffer cells contributes to progression of nonalcoholic steatohepatitis[J]. J Clin Invest,2019,129(2):546-555. [31] Devkota S,Wang Y,Musch M W,et al. Dietary-fat-induced taurocholic acid promotespathobiont expansion and colitis in Il10-/- mice[J]. Nature,2012,487(7405):104-108. doi: 10.1038/nature11225 [32] Jones B V,Begley M,Hill C,et al. Functional and comparative metagenomic analysisof bile salt hydrolase activity in the human gut microbiome[J]. Proc Natl Acad Sci US A,2008,105(36):13580-13585. doi: 10.1073/pnas.0804437105 [33] Sayin S I,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 [34] Ridaura V K,Faith J J,Rey F E,et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice[J]. Science,2013,341(6150):1241214. doi: 10.1126/science.1241214 [35] Parséus A,Sommer N,Sommer F,et al. Microbiota-induced obesity requires farnesoid X receptor[J]. Gut,2017,66(3):429-437. doi: 10.1136/gutjnl-2015-310283 [36] Jiang C,Xie C,Li F,et al. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease[J]. J Clin Invest,2015,125(1):386-402. doi: 10.1172/JCI76738 [37] Selwyn F P,Csanaky I L,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 [38] Sutti S,Bruzzì S,Albano E. The role of immune mechanisms in alcoholic and nonalcoholic steatohepatitis: A 2015 update[J]. Expert Rev Gastroenterol Hepatol,2016,10(2):243-253. doi: 10.1586/17474124.2016.1111758 [39] Biagioli M,Carino A. Signaling from intestine to the host: How bile acids regulate intestinal and liver immunity[J]. Handb Exp Pharmacol,2019,256:95-108. [40] Gai Z,Gui T,Alecu I,et al. Farnesoid X receptor activation induces the degradation of hepatotoxic 1-deoxysphingolipids in non-alcoholic fatty liver disease[J]. Liver Int,2020,40(4):844-859. doi: 10.1111/liv.14340 [41] Guo C,Xie S,Chi Z,et al. Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome[J]. Immunity,2016,45(4):802-816. doi: 10.1016/j.immuni.2016.09.008 [42] Shi Y,Su W,Zhang L,et al. TGR5 regulates macrophage inflammation in nonalcoholic steatohepatitis by modulating NLRP3 inflammasome activation[J]. Front Immunol,2021,11:609060. doi: 10.3389/fimmu.2020.609060 [43] Lallukka S,Sädevirta S,Kallio M T,et al. Predictors of liver fat and stiffness in nonalcoholic fatty liver disease (NAFLD) - an 11-year prospective study[J]. Sci Rep,2017,7(1):14561. doi: 10.1038/s41598-017-14706-0 [44] Eslam M,Mangia A,Berg T,et al. Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes[J]. Hepatology,2016,64(1):34-46. doi: 10.1002/hep.28475
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