{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:38:35Z","timestamp":1772771915078,"version":"3.50.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Natural Science Foundation of Tianjin Bureau of traditional Chinese Medicine","award":["13040"],"award-info":[{"award-number":["13040"]}]},{"name":"Key project of Tianjin science and technology support plan","award":["14ZCZDSY00021"],"award-info":[{"award-number":["14ZCZDSY00021"]}]},{"name":"Foundation of Tianjin Clinical Medical Research Center of Acute Abdomen with integrated Chinese and Western medicine","award":["15ZXLCSY00030"],"award-info":[{"award-number":["15ZXLCSY00030"]}]},{"name":"Project of the national science and technology program of Ministry of human resources and social security","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Project of Tianjin thousands of people plan","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lipids Health Dis"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Many studies indicate that gallstone formation has genetic components. The abnormal expression of lipid-related genes could be the basis for particular forms of cholesterol gallstone disease. The aim of this study was to obtain insight into lipid metabolism disorder during cholesterol gallstone formation and to evaluate the effect of ursodeoxycholic acid (UDCA) on the improvement of bile lithogenicity and its potential influence on the transcription of lipid-related genes.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Gallstone-susceptible mouse models were induced by feeding with a lithogenic diet (LD) for 8\u2009weeks. Bile and liver tissues were obtained from these mouse models after 0, 4 and 8\u2009weeks. Bile lipids were measured enzymatically, and the cholesterol saturation index (CSI) was calculated to evaluate the bile lithogenicity by using Carey\u2019s critical tables. Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of farnesoid X receptor (FXR), liver X receptor (LXR), adenosine triphosphate-binding cassette subfamily G member 5\/8 (ABCG5\/8), cholesterol 7-\u03b1 hydroxylase (CYP7A1), oxysterol 7-\u03b1 hydroxylase (CYP7B1), sterol 27-\u03b1 hydroxylase (CYP27A1), peroxisome proliferator-activated receptor alpha (PPAR-\u03b1) and adenosine triphosphate-binding cassette subfamily B member 11 (ABCB11).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The rate of gallstone formation was 100% in the 4-week group but only 30% in the UDCA-treated group. The UDCA-treated group had a significantly lower CSI compared with other groups. Of special note, the data on the effects of UDCA showed higher expression levels of ABCG8, ABCB11 and CYP27A1, as well as lower expression levels of LXR and PPAR-\u03b1, compared to the model control group.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>UDCA exhibits tremendously potent activity in restraining lipid accumulation, thus reversing the lithogenic effect and protecting hepatocytes from serious pathological damage. The abnormal expression of ABCG8, CYP7A1, CYP27A1, LXR and PPAR-\u03b1 might lead to high lithogenicity of bile. These results are helpful in exploring new lipid metabolism pathways and potential targets for the treatment of cholesterol stones and for providing some basis for the study of the pathogenesis and genetic characteristics of cholelithiasis. Research on the mechanism of UDCA in improving lipid metabolism and bile lithogenicity may be helpful for clinical treatment and for reducing the incidence of gallstones.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12944-020-01334-3","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T12:23:29Z","timestamp":1593692609000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The effect of ursodeoxycholic acid on the relative expression of the lipid metabolism genes in mouse cholesterol gallstone models"],"prefix":"10.1186","volume":"19","author":[{"given":"Ning","family":"Fan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoying","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanning","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6415-0321","authenticated-orcid":false,"given":"Yunfeng","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"1334_CR1","doi-asserted-by":"crossref","first-page":"e115145","DOI":"10.1371\/journal.pone.0115145","volume":"9","author":"YC Chen","year":"2014","unstructured":"Chen YC, Chiou C, Lin MN, Lin CL. The prevalence and risk factors for gallstone disease in taiwanese vegetarians. PLoS One. 2014;9:e115145.","journal-title":"PLoS One"},{"key":"1334_CR2","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/S0016-5085(98)70266-5","volume":"115","author":"JF Miquel","year":"1998","unstructured":"Miquel JF, Covarrubias C, Villaroel L, Mingrone G, Greco AV, Puglielli L, et al. Genetic epidemiology of cholesterol cholelithiasis among chilean hispanics, amerindians, and maoris. Gastroenterology. 1998;115:937\u201346.","journal-title":"Gastroenterology"},{"key":"1334_CR3","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s10552-014-0458-3","volume":"25","author":"Y Gong","year":"2014","unstructured":"Gong Y, Li S, Tang Y, Mai C, Ba M, Jiang P, et al. Cholelithiasis and risk of pancreatic cancer: systematic review and meta-analysis of 21 observational studies. Cancer Causes Control. 2014;25:1543\u201351.","journal-title":"Cancer Causes Control"},{"key":"1334_CR4","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1053\/j.gastro.2010.10.060","volume":"140","author":"CE Ruhl","year":"2011","unstructured":"Ruhl CE, Everhart JE. Gallstone disease is associated with increased mortality in the United States. Gastroenterology. 2011;140:508\u201316.","journal-title":"Gastroenterology"},{"key":"1334_CR5","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nm1785","volume":"14","author":"SB Biddinger","year":"2008","unstructured":"Biddinger SB, Haas JT, Yu BB, Bezy O, Jing E, Zhang W, et al. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med. 2008;14:778\u201382.","journal-title":"Nat Med"},{"key":"1334_CR6","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/ajg.2016.141","volume":"111","author":"YC Chen","year":"2016","unstructured":"Chen YC, Chang CC, Liu KL. Mirizzi syndrome due to a large radiolucent gallstone. Am J Gastroenterol. 2016;111:599.","journal-title":"Am J Gastroenterol"},{"issue":"Suppl 1","key":"1334_CR7","doi-asserted-by":"crossref","first-page":"S124","DOI":"10.1016\/j.jhep.2008.01.012","volume":"48","author":"F Lammert","year":"2008","unstructured":"Lammert F, Miquel JF. Gallstone disease: from genes to evidence-based therapy. J Hepatol. 2008;48(Suppl 1):S124\u201335.","journal-title":"J Hepatol"},{"key":"1334_CR8","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1042\/BC20040088","volume":"97","author":"KJ van Erpecum","year":"2005","unstructured":"van Erpecum KJ. Biliary lipids, water and cholesterol gallstones. Biol Cell. 2005;97:815\u201322.","journal-title":"Biol Cell"},{"key":"1334_CR9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1136\/gut.34.1.110","volume":"34","author":"Z Halpern","year":"1993","unstructured":"Halpern Z, Moshkowitz M, Laufer H, Peled Y, Gilat T. Effect of phospholipids and their molecular species on cholesterol solubility and nucleation in human and model biles. Gut. 1993;34:110\u20135.","journal-title":"Gut"},{"key":"1334_CR10","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1001\/jama.2014.12014","volume":"314","author":"BM Wolfe","year":"2015","unstructured":"Wolfe BM, Gardiner B, Frey CF. Laparoscopic cholecystectomy: a remarkable development. JAMA. 2015;314:1406.","journal-title":"JAMA"},{"key":"1334_CR11","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/s00464-016-5011-x","volume":"31","author":"CS Loozen","year":"2017","unstructured":"Loozen CS, Oor JE, van Ramshorst B, van Santvoort HC, Boerma D. Conservative treatment of acute cholecystitis: a systematic review and pooled analysis. Surg Endosc. 2017;31:504\u201315.","journal-title":"Surg Endosc"},{"key":"1334_CR12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/1440-1681.12490","volume":"43","author":"M Hu","year":"2016","unstructured":"Hu M, Fok BS, Wo SK, Lee VH, Zuo Z, Tomlinson B. Effect of common polymorphisms of the farnesoid x receptor and bile acid transporters on the pharmacokinetics of ursodeoxycholic acid. Clin Exp Pharmacol Physiol. 2016;43:34\u201340.","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"1334_CR13","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1042\/CS20110184","volume":"121","author":"MG Roma","year":"2011","unstructured":"Roma MG, Toledo FD, Boaglio AC, Basiglio CL, Crocenzi FA, Sanchez PE. Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications. Clin Sci (Lond). 2011;121:523\u201344.","journal-title":"Clin Sci (Lond)"},{"key":"1334_CR14","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/labinvest.2014.140","volume":"95","author":"Y Chen","year":"2015","unstructured":"Chen Y, Kong J, Wu S. Cholesterol gallstone disease: focusing on the role of gallbladder. Lab Investig. 2015;95:124\u201331.","journal-title":"Lab Investig"},{"key":"1334_CR15","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1136\/gut.2006.109934","volume":"56","author":"MP Guarino","year":"2007","unstructured":"Guarino MP, Cong P, Cicala M, Alloni R, Carotti S, Behar J. Ursodeoxycholic acid improves muscle contractility and inflammation in symptomatic gallbladders with cholesterol gallstones. Gut. 2007;56:815\u201320.","journal-title":"Gut."},{"key":"1334_CR16","doi-asserted-by":"crossref","first-page":"e12935","DOI":"10.1111\/eci.12935","volume":"48","author":"C Rebholz","year":"2018","unstructured":"Rebholz C, Krawczyk M, Lammert F. Genetics of gallstone disease. Eur J Clin Investig. 2018;48:e12935.","journal-title":"Eur J Clin Investig"},{"key":"1334_CR17","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1755-5922.2008.00062.x","volume":"26","author":"J Beltowski","year":"2008","unstructured":"Beltowski J. Liver x receptors (lxr) as therapeutic targets in dyslipidemia. Cardiovasc Ther. 2008;26:297\u2013316.","journal-title":"Cardiovasc Ther"},{"key":"1334_CR18","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.1016\/j.bmc.2016.06.039","volume":"24","author":"DD Yu","year":"2016","unstructured":"Yu DD, Andrali SS, Li H, Lin M, Huang W, Forman BM. Novel fxr (farnesoid x receptor) modulators: potential therapies for cholesterol gallstone disease. Bioorgan Med Chem. 2016;24:3986\u201393.","journal-title":"Bioorgan Med Chem"},{"key":"1334_CR19","doi-asserted-by":"crossref","first-page":"322","DOI":"10.5483\/BMBRep.2013.46.6.246","volume":"46","author":"SS Back","year":"2013","unstructured":"Back SS, Kim J, Choi D, Lee ES, Choi SY, Han K. Cooperative transcriptional activation of atp-binding cassette sterol transporters abcg5 and abcg8 genes by nuclear receptors including liver-x-receptor. BMB Rep. 2013;46:322\u20137.","journal-title":"BMB Rep"},{"key":"1334_CR20","doi-asserted-by":"crossref","first-page":"48275","DOI":"10.1074\/jbc.M310223200","volume":"278","author":"GA Graf","year":"2003","unstructured":"Graf GA, Yu L, Li WP, Gerard R, Tuma PL, Cohen JC, et al. Abcg5 and abcg8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J Biol Chem. 2003;278:48275\u201382.","journal-title":"J Biol Chem"},{"key":"1334_CR21","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1016\/j.jacc.2013.12.055","volume":"63","author":"S Stender","year":"2014","unstructured":"Stender S, Frikke-Schmidt R, Nordestgaard BG, Tybjaerg-Hansen A. The abcg5\/8 cholesterol transporter and myocardial infarction versus gallstone disease. J Am Coll Cardiol. 2014;63:2121\u20138.","journal-title":"J Am Coll Cardiol"},{"key":"1334_CR22","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0022-2275(20)40677-7","volume":"19","author":"MC Carey","year":"1978","unstructured":"Carey MC. Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res. 1978;19:945.","journal-title":"J Lipid Res"},{"key":"1334_CR23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2017.10.003","volume":"815","author":"M Liu","year":"2017","unstructured":"Liu M, Liu C, Chen H, Huang X, Zeng X, Zhou J, et al. Prevention of cholesterol gallstone disease by schaftoside in lithogenic diet-induced c57bl\/6 mouse model. Eur J Pharmacol. 2017;815:1\u201309.","journal-title":"Eur J Pharmacol"},{"key":"1334_CR24","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.jacc.2014.02.553","volume":"63","author":"W Hancock-Cerutti","year":"2014","unstructured":"Hancock-Cerutti W, Rader DJ. Opposing effects of abcg5\/8 function on myocardial infarction and gallstone disease. J Am Coll Cardiol. 2014;63:2129\u201330.","journal-title":"J Am Coll Cardiol"},{"key":"1334_CR25","doi-asserted-by":"crossref","first-page":"18793","DOI":"10.1074\/jbc.M109927200","volume":"277","author":"JJ Repa","year":"2002","unstructured":"Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ. Regulation of atp-binding cassette sterol transporters abcg5 and abcg8 by the liver x receptors alpha and beta. J Biol Chem. 2002;277:18793\u2013800.","journal-title":"J Biol Chem"},{"key":"1334_CR26","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1172\/JCI0216001","volume":"110","author":"L Yu","year":"2002","unstructured":"Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC, et al. Overexpression of abcg5 and abcg8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest. 2002;110:671\u201380.","journal-title":"J Clin Invest"},{"key":"1334_CR27","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/hep.28570","volume":"64","author":"HH Wang","year":"2016","unstructured":"Wang HH, Li X, Patel SB, Wang DQ. Evidence that the adenosine triphosphate-binding cassette g5\/g8-independent pathway plays a determinant role in cholesterol gallstone formation in mice. Hepatology. 2016;64:853\u201364.","journal-title":"Hepatology"},{"key":"1334_CR28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.taap.2014.12.005","volume":"283","author":"P Song","year":"2015","unstructured":"Song P, Rockwell CE, Cui JY, Klaassen CD. Individual bile acids have differential effects on bile acid signaling in mice. Toxicol Appl Pharm. 2015;283:57\u201364.","journal-title":"Toxicol Appl Pharm"},{"key":"1334_CR29","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/hep.28570","volume":"64","author":"HH Wang","year":"2016","unstructured":"Wang HH, Li X, Patel SB, Wang DQH. Evidence that the adenosine triphosphate-binding cassette g5\/g8-independent pathway plays a determinant role in cholesterol gallstone formation in mice. Hepatology. 2016;64:853\u201364.","journal-title":"Hepatology"},{"key":"1334_CR30","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/383728a0","volume":"383","author":"BA Janowski","year":"1996","unstructured":"Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor lxr alpha. Nature. 1996;383:728\u201331.","journal-title":"Nature"},{"key":"1334_CR31","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.apsb.2019.02.004","volume":"9","author":"L Sun","year":"2019","unstructured":"Sun L, Pang Y, Wang X, Wu Q, Liu H, Liu B, et al. Ablation of gut microbiota alleviates obesity-induced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters. Acta Pharm Sin B. 2019;9:702\u201310.","journal-title":"Acta Pharm Sin B"},{"key":"1334_CR32","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/hep.27744","volume":"62","author":"NS Ghonem","year":"2015","unstructured":"Ghonem NS, Assis DN, Boyer JL. Fibrates and cholestasis. Hepatology. 2015;62:635\u201343.","journal-title":"Hepatology"},{"key":"1334_CR33","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1126\/science.284.5418.1362","volume":"284","author":"M Makishima","year":"1999","unstructured":"Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, et al. Identification of a nuclear receptor for bile acids. Science. 1999;284:1362\u20135.","journal-title":"Science"},{"key":"1334_CR34","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0092-8674(00)80763-1","volume":"97","author":"DW Russell","year":"1999","unstructured":"Russell DW. Nuclear orphan receptors control cholesterol catabolism. Cell. 1999;97:539\u201342.","journal-title":"Cell"},{"key":"1334_CR35","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/hep.24107","volume":"53","author":"T Li","year":"2011","unstructured":"Li T, Matozel M, Boehme S, Kong B, Nilsson LM, Guo G, et al. Overexpression of cholesterol 7alpha-hydroxylase promotes hepatic bile acid synthesis and secretion and maintains cholesterol homeostasis. Hepatology. 2011;53:996\u20131006.","journal-title":"Hepatology"},{"key":"1334_CR36","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0022-2275(20)32398-1","volume":"41","author":"M Marrapodi","year":"2000","unstructured":"Marrapodi M, Chiang JY. Peroxisome proliferator-activated receptor alpha (pparalpha) and agonist inhibit cholesterol 7alpha-hydroxylase gene (cyp7a1) transcription. J Lipid Res. 2000;41:514\u201320.","journal-title":"J Lipid Res"},{"key":"1334_CR37","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1161\/hq1101.098228","volume":"21","author":"SM Post","year":"2001","unstructured":"Post SM, Duez H, Gervois PP, Staels B, Kuipers F, Princen HM. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression. Arterioscler Thromb Vasc Biol. 2001;21:1840\u20135.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"1334_CR38","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1194\/jlr.M800645-JLR200","volume":"50","author":"Y Xie","year":"2009","unstructured":"Xie Y, Newberry EP, Kennedy SM, Luo J, Davidson NO. Increased susceptibility to diet-induced gallstones in liver fatty acid binding protein knockout mice. J Lipid Res. 2009;50:977\u201387.","journal-title":"J Lipid Res"},{"key":"1334_CR39","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1210\/me.2007-0113","volume":"21","author":"SM Houten","year":"2007","unstructured":"Houten SM, Volle DH, Cummins CL, Mangelsdorf DJ, Auwerx J. In vivo imaging of farnesoid x receptor activity reveals the ileum as the primary bile acid signaling tissue. Mol Endocrinol. 2007;21:1312\u201323.","journal-title":"Mol Endocrinol"},{"key":"1334_CR40","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1038\/sj.emboj.7601049","volume":"25","author":"SM Houten","year":"2006","unstructured":"Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J. 2006;25:1419\u201325.","journal-title":"EMBO J"},{"key":"1334_CR41","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1507\/endocrj.KR07E-002","volume":"55","author":"S Fukumoto","year":"2008","unstructured":"Fukumoto S. Actions and mode of actions of fgf19 subfamily members. Endocr J. 2008;55:23\u201331.","journal-title":"Endocr J"},{"key":"1334_CR42","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1111\/bph.14705","volume":"176","author":"Y Zhang","year":"2019","unstructured":"Zhang Y, Jiang R, Zheng X, Lei S, Huang F, Xie G, et al. Ursodeoxycholic acid accelerates bile acid enterohepatic circulation. Brit J Pharmacol. 2019;176:2848\u201363.","journal-title":"Brit J Pharmacol"},{"key":"1334_CR43","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.jhep.2014.12.034","volume":"62","author":"M Mueller","year":"2015","unstructured":"Mueller M, Thorell A, Claudel T, Jha P, Koefeler H, Lackner C, et al. Ursodeoxycholic acid exerts farnesoid x receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. J Hepatol. 2015;62:1398\u2013404.","journal-title":"J Hepatol"},{"key":"1334_CR44","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1038\/s41591-018-0222-4","volume":"24","author":"L Sun","year":"2018","unstructured":"Sun L, Xie C, Wang G, Wu Y, Wu Q, Wang X, et al. Gut microbiota and intestinal fxr mediate the clinical benefits of metformin. Nat Med. 2018;24:1919\u201329.","journal-title":"Nat Med"},{"key":"1334_CR45","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.clinre.2012.06.006","volume":"36","author":"R Kubitz","year":"2012","unstructured":"Kubitz R, Dr\u00f6ge C, Stindt J, Weissenberger K, H\u00e4ussinger D. The bile salt export pump (bsep) in health and disease. Clin Res Hepatol Gas. 2012;36:536\u201353.","journal-title":"Clin Res Hepatol Gas"},{"key":"1334_CR46","doi-asserted-by":"crossref","first-page":"8330","DOI":"10.1128\/MCB.00852-07","volume":"27","author":"C Mataki","year":"2007","unstructured":"Mataki C, Magnier BC, Houten SM, Annicotte J, Argmann C, Thomas C, et al. Compromised intestinal lipid absorption in mice with a liver-specific deficiency of liver receptor homolog 1. Mol Cell Biol. 2007;27:8330\u20139.","journal-title":"Mol Cell Biol"},{"key":"1334_CR47","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1002\/hep.23151","volume":"50","author":"J Weerachayaphorn","year":"2009","unstructured":"Weerachayaphorn J, Cai S, Soroka CJ, Boyer JL. Nf-e2- related factor 2 (nrf2) is a positive regulator of human bile salt export pump (bsep) expression. Hepatology. 2009;50:1588\u201396.","journal-title":"Hepatology"},{"key":"1334_CR48","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1365-2362.2010.02300.x","volume":"40","author":"HH Wang","year":"2010","unstructured":"Wang HH, Lammert F, Schmitz A, Wang DQ. Transgenic overexpression of abcb11 enhances biliary bile salt outputs, but does not affect cholesterol cholelithogenesis in mice. Eur J Clin Investig. 2010;40:541\u201351.","journal-title":"Eur J Clin Investig"},{"key":"1334_CR49","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1152\/ajpgi.00322.2012","volume":"304","author":"AS Henkel","year":"2013","unstructured":"Henkel AS, Karin ERG, Havinga R, Boverhof R, Green RM, Verkade HJ. Hepatic overexpression of abcb11 in mice promotes the conservation of bile acids within the enterohepatic circulation. Am J Physiol Gastrointest Liver Physiol. 2013;304:221\u20136.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"1334_CR50","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1124\/pr.113.008201","volume":"66","author":"T Li","year":"2014","unstructured":"Li T, Chiang JY. Bile acid signaling in metabolic disease and drug therapy. Pharmacol Rev. 2014;66:948\u201383.","journal-title":"Pharmacol Rev"},{"key":"1334_CR51","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-0031-1276645","volume":"31","author":"M Krawczyk","year":"2011","unstructured":"Krawczyk M, Wang DQ, Portincasa P, Lammert F. Dissecting the genetic heterogeneity of gallbladder stone formation. Semin Liver Dis. 2011;31:157\u201372.","journal-title":"Semin Liver Dis"},{"key":"1334_CR52","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1053\/gast.2001.20878","volume":"120","author":"F Lammert","year":"2001","unstructured":"Lammert F, Carey MC, Paigen B. Chromosomal organization of candidate genes involved in cholesterol gallstone formation: a murine gallstone map. Gastroenterology. 2001;120:221\u201338.","journal-title":"Gastroenterology."}],"container-title":["Lipids in Health and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12944-020-01334-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12944-020-01334-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12944-020-01334-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T23:26:10Z","timestamp":1625181970000},"score":1,"resource":{"primary":{"URL":"https:\/\/lipidworld.biomedcentral.com\/articles\/10.1186\/s12944-020-01334-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,2]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1334"],"URL":"https:\/\/doi.org\/10.1186\/s12944-020-01334-3","relation":{},"ISSN":["1476-511X"],"issn-type":[{"value":"1476-511X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,2]]},"assertion":[{"value":"12 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All procedures conformed to the National Institutes of Health guidelines and were approved by the Animal Care and Use Committee in Tianjin Nankai Hospital.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.ik","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"158"}}