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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.5 P.414-427

http://doi.org/10.1631/jzus.B1900158


Bile-ology: from bench to bedside


Author(s):  Li-Hua Jin, Zhi-Peng Fang, Min-Jie Fan, Wen-Dong Huang

Affiliation(s):  Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; more

Corresponding email(s):   whuang@coh.org

Key Words:  Bile acid, Gut microbiota, Farnesoid X receptor, G protein-coupled bile acid receptor, Metabolic disease


Li-Hua Jin, Zhi-Peng Fang, Min-Jie Fan, Wen-Dong Huang. Bile-ology: from bench to bedside[J]. Journal of Zhejiang University Science B, 2019, 20(5): 414-427.

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DOI - 10.1631/jzus.B1900158


Abstract: 
bile acids (BAs) are originally known as detergents essential for the digestion and absorption of lipids. In recent years, extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes, including glucose and lipid metabolism, energy expenditure, inflammation, tumorigenesis, cardiovascular disease, and even the central nervous system in addition to cholesterol homeostasis, enterohepatic protection and liver regeneration. BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs. The signaling actions of BAs can also be mediated through specific nuclear receptors and membrane-bound G protein-coupled receptors. Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling. In this mini-review, we summarize recent advances in bile-ology, focusing on its translational studies.

胆汁学:从研究到临床

概要:胆汁酸广为人知的功能是帮助脂类的消化和吸收.近几年的大量研究表明:胆汁酸除了在胆固醇代谢平衡、肝肠循环以及调节肝脏再生等方面的作用以外,还可以作为一类肠道激素调节机体的生理和病理反应,包括糖脂代谢、能量消耗、炎症、肿瘤、心血管疾病和神经系统疾病等.胆汁酸与肠道菌群关系密切,这可能也是其在各器官中发挥重要功能的原因之一.胆汁酸调节的信号主要通过其特异的胆酸核受体与G蛋白偶联的胆酸膜受体进行调节.研究表明一些药理制剂或者外科减肥手术在代谢性疾病中的疗效也是通过靶向胆汁酸信号实现的.本文主要总结了胆汁学最新的研究进展,重点关注了与胆汁酸信号通路调节相关的转化医学研究进展.
关键词:胆汁酸;肠道菌群;法尼醇受体;G蛋白偶联胆汁酸受体;代谢性疾病

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Bárcena C, Quirós PM, Durand S, et al., 2018. Methionine restriction extends lifespan in progeroid mice and alters lipid and bile acid metabolism. Cell Rep, 24(9):2392-2403.

[2]Bechmann LP, Kocabayoglu P, Sowa JP, et al., 2013. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis. Hepatology, 57(4):1394-1406.

[3]Bertaggia E, Jensen KK, Castro-Perez J, et al., 2017. Cyp8b1 ablation prevents Western diet-induced weight gain and hepatic steatosis because of impaired fat absorption. Am J Physiol Endocrinol Metab, 313(2):E121-E133.

[4]Beysen C, Murphy EJ, Deines K, et al., 2012. Effect of bile acid sequestrants on glucose metabolism, hepatic de novo lipogenesis, and cholesterol and bile acid kinetics in type 2 diabetes: a randomised controlled study. Diabetologia, 55(2):432-442.

[5]Biemann R, Penner M, Borucki K, et al., 2016. Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial. Sci Rep, 6:30173.

[6]Blokker BA, Maijo M, Echeandia M, et al., 2019. Fine-tuning of sirtuin 1 expression is essential to protect the liver from cholestatic liver disease. Hepatology, 69(2):699-716.

[7]Broeders EPM, Nascimento EBM, Havekes B, et al., 2015. The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab, 22(3):418-426.

[8]Browning MG, Pessoa BM, Khoraki J, et al., 2019. Changes in bile acid metabolism, transport, and signaling as central drivers for metabolic improvements after bariatric surgery. Curr Obes Rep, Epub ahead of print.

[9]Byun S, Kim DH, Ryerson D, et al., 2018. Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis. Nat Commun, 9(1):2590.

[10]Camilleri M, Gores GJ, 2015. Therapeutic targeting of bile acids. Am J Physiol Gastrointest Liver Physiol, 309(4):G209-G215.

[11]Carr RM, Reid AE, 2015. FXR agonists as therapeutic agents for non-alcoholic fatty liver disease. Curr Atheroscler Rep, 17(4):16.

[12]Castellano JM, Guinda A, Delgado T, et al., 2013. Biochemical basis of the antidiabetic activity of oleanolic acid and related pentacyclic triterpenes. Diabetes, 62(6):1791-1799.

[13]Chávez-Talavera O, Tailleux A, Lefebvre P, et al., 2017. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology, 152(7):1679-1694.e3.

[14]Chen JZ, Thomsen M, Vitetta L, 2019. Interaction of gut microbiota with dysregulation of bile acids in the pathogenesis of nonalcoholic fatty liver disease and potential therapeutic implications of probiotics. J Cell Biochem, 120(3):2713-2720.

[15]Chen WD, Yu D, Forman BM, et al., 2013. Deficiency of G-protein-coupled bile acid receptor Gpbar1 (TGR5) enhances chemically induced liver carcinogenesis. Hepatology, 57(2):656-666.

[16]Chianese G, Golin-Pacheco SD, Taglialatela-Scafati O, et al., 2019. Bioactive triterpenoids from the caffeine-rich plants guayusa and maté. Food Res Int, 115:504-510.

[17]Chiang JYL, Ferrell JM, 2018. Bile acid metabolism in liver pathobiology. Gene Expr, 18(2):71-87.

[18]de Aguiar Vallim TQ, Tarling EJ, Ahn H, et al., 2015. MAFG is a transcriptional repressor of bile acid synthesis and metabolism. Cell Metab, 21(2):298-310.

[19]Devkota S, Wang YW, Musch MW, et al., 2012. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in il10−/− mice. Nature, 487(7405):104-108.

[20]Ding LL, Yang L, Wang ZT, et al., 2015. Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharm Sin B, 5(2):135-144.

[21]Ding LL, Sousa KM, Jin LH, et al., 2016. Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology, 64(3):760-773.

[22]Donkers JM, Roscam Abbing RLP, van de Graaf SFJ, 2019. Developments in bile salt based therapies: a critical overview. Biochem Pharmacol, 161:1-13.

[23]Downes M, Verdecia MA, Roecker AJ, et al., 2003. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell, 11(4):1079-1092.

[24]Duboc H, Rajca S, Rainteau D, et al., 2013. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut, 62(4):531-539.

[25]Duboc H, Taché Y, Hofmann AF, 2014. The bile acid TGR5 membrane receptor: from basic research to clinical application. Dig Liver Dis, 46(4):302-312.

[26]Esser N, Legrand-Poels S, Piette J, et al., 2014. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract, 105(2):141-150.

[27]Falony G, Joossens M, Vieira-Silva S, et al., 2016. Population-level analysis of gut microbiome variation. Science, 352(6285):560-564.

[28]Feng S, Yang MM, Zhang ZS, et al., 2009. Identification of an N-oxide pyridine GW4064 analog as a potent FXR agonist. Bioorg Med Chem Lett, 19(9):2595-2598.

[29]Ferrell JM, Pathak P, Boehme S, et al., 2019. Deficiency of both farnesoid X receptor and Takeda G protein-coupled receptor 5 exacerbated liver fibrosis in mice. Hepatology,

[30]Finn PD, Rodriguez D, Kohler J, et al., 2019. Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice. Am J Physiol Gastrointest Liver Physiol, 316(3):G412-G424.

[31]Flatt B, Martin R, Wang TL, et al., 2009. Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR). J Med Chem, 52(4):904-907.

[32]Franzosa EA, Sirota-Madi A, Avila-Pacheco J, et al., 2019. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat Microbiol, 4(2):293-305.

[33]Genet C, Strehle A, Schmidt C, et al., 2010. Structure-activity relationship study of betulinic acid, a novel and selective TGR5 agonist, and its synthetic derivatives: potential impact in diabetes. J Med Chem, 53(1):178-190.

[34]Gerhard GS, Styer AM, Wood GC, et al., 2013. A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass. Diabetes Care, 36(7):1859-1864.

[35]Golay A, Ybarra J, 2005. Link between obesity and type 2 diabetes. Best Pract Res Clin Endocrinol Metab, 19(4):649-663.

[36]Guo C, Chen WD, Wang YD, 2016. TGR5, not only a metabolic regulator. Front Physiol, 7:646.

[37]Guo CS, Xie SJ, Chi ZX, et al., 2016. Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome. Immunity, 45(4):802-816.

[38]Haeusler RA, Astiarraga B, Camastra S, et al., 2013. Human insulin resistance is associated with increased plasma levels of 12α-hydroxylated bile acids. Diabetes, 62(12):4184-4191.

[39]Halmy L, Fehér T, Steczek K, et al., 1986. High serum bile acid level in obesity: its decrease during and after total fasting. Acta Med Hung, 43(1):55-58.

[40]Hansen M, Sonne DP, Mikkelsen KH, et al., 2017. Bile acid sequestrants for glycemic control in patients with type 2 diabetes: a systematic review with meta-analysis of randomized controlled trials. J Diabetes Complications, 31(5):918-927.

[41]He FT, Li J, Mu Y, et al., 2006. Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells. Circ Res, 98(2):192-199.

[42]Hegyi P, Maléth J, Walters JR, et al., 2018. Guts and gall: bile acids in regulation of intestinal epithelial function in health and disease. Physiol Rev, 98(4):1983-2023.

[43]Hodge RJ, Nunez DJ, 2016. Therapeutic potential of Takeda-G-protein-receptor-5 (TGR5) agonists. Hope or hype? Diabetes Obes Metab, 18(5):439-443.

[44]Hodge RJ, Lin J, Vasist Johnson LS, et al., 2013. Safety, pharmacokinetics, and pharmacodynamic effects of a selective TGR5 agonist, SB-756050, in type 2 diabetes. Clin Pharmacol Drug Dev, 2(3):213-222.

[45]Inagaki T, Moschetta A, Lee YK, et al., 2006. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci USA, 103(10):3920-3925.

[46]Jia W, Xie GX, Jia WP, 2018. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol, 15(2):111-128.

[47]Jiao N, Baker SS, Chapa-Rodriguez A, et al., 2018. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD. Gut, 67(10):1881-1891.

[48]Jin LH, Li Y, 2010. Structural and functional insights into nuclear receptor signaling. Adv Drug Deliv Rev, 62(13):1218-1226.

[49]Jin LH, Feng XH, Rong H, et al., 2013. The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. Nat Commun, 4:1937.

[50]Jin LH, Wang R, Zhu YL, et al., 2015. Selective targeting of nuclear receptor FXR by avermectin analogues with therapeutic effects on nonalcoholic fatty liver disease. Sci Rep, 5:17288.

[51]Jones ML, Martoni CJ, Ganopolsky JG, et al., 2014. The human microbiome and bile acid metabolism: dysbiosis, dysmetabolism, disease and intervention. Expert Opin Biol Ther, 14(4):467-482.

[52]Kaur A, Patankar JV, de Haan W, et al., 2015. Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1. Diabetes, 64(4):1168-1179.

[53]Keitel V, Häussinger D, 2011. TGR5 in the biliary tree. Dig Dis, 29(1):45-47.

[54]Kemper JK, Xiao Z, Ponugoti B, et al., 2009. FXR acetylation is normally dynamically regulated by p300 and SIRT1 but constitutively elevated in metabolic disease states. Cell Metab, 10(5):392-404.

[55]Kim I, Morimura K, Shah Y, et al., 2007. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis, 28(5):940-946.

[56]Kobayashi M, Ikegami H, Fujisawa T, et al., 2007. Prevention and treatment of obesity, insulin resistance, and diabetes by bile acid-binding resin. Diabetes, 56(1):239-247.

[57]Kuhre RE, Wewer Albrechtsen NJ, Larsen O, et al., 2018. Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas. Mol Metab, 11:84-95.

[58]Kuipers F, Groen AK, 2017. An unexpected role for bile acid synthesis in adaptation to low temperature. Nat Med, 23(7):800-802.

[59]Kurdi P, Kawanishi K, Mizutani K, et al., 2006. Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria. J Bacteriol, 188(5):1979-1986.

[60]Laffitte B, Liu B, Kim Y, et al., 2017. Development of LMB763, a novel, orally bioavailable, clinical farnesoid X receptor agonist for the treatment of non-alcoholic steatohepatitis and hepatobiliary disorders. J Hepatol, 66(S1):S166.

[61]Lee CK, Jeong SH, Jang C, et al., 2019. Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation. Science, 363(6427):644-649.

[62]Li F, Jiang CT, Krausz KW, et al., 2013. Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat Commun, 4:2384.

[63]Li TG, Chiang JY, 2014. Bile acid signaling in metabolic disease and drug therapy. Pharmacol Rev, 66(4):948-983.

[64]Liu XJ, Zhang XW, Ji LL, et al., 2015. Farnesoid X receptor associates with β-catenin and inhibits its activity in hepatocellular carcinoma. Oncotarget, 6(6):4226-4238.

[65]https://doi.org/10.18632/oncotarget.2899

[66]Lo SH, Li YX, Cheng KC, et al., 2017. Ursolic acid activates the TGR5 receptor to enhance GLP-1 secretion in type 1-like diabetic rats. Naunyn Schmiedebergs Arch Pharmacol, 390(11):1097-1104.

[67]Lu Y, Zheng WL, Lin SC, et al., 2018. Identification of an oleanane-type triterpene hedragonic acid as a novel farnesoid X receptor ligand with liver protective effects and anti-inflammatory activity. Mol Pharmacol, 93(2):63-72.

[68]Ma C, Han MJ, Heinrich B, et al., 2018. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science, 360(6391):eaan5931.

[69]Maghsoodi N, Shaw N, Cross GF, et al., 2019. Bile acid metabolism is altered in those with insulin resistance after gestational diabetes mellitus. Clin Biochem, 64:12-17.

[70]Mahmoud AA, Elshazly SM, 2014. Ursodeoxycholic acid ameliorates fructose-induced metabolic syndrome in rats. PLoS ONE, 9(9):e106993.

[71]Maruyama T, Miyamoto Y, Nakamura T, et al., 2002. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun, 298(5):714-719.

[72]Matysik S, Martin J, Bala M, et al., 2011. Bile acid signaling after an oral glucose tolerance test. Chem Phys Lipids, 164(6):525-529.

[73]McGavigan AK, Garibay D, Henseler ZM, et al., 2017. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut, 66(2):226-234.

[74]Mertens KL, Kalsbeek A, Soeters MR, et al., 2017. Bile acid signaling pathways from the enterohepatic circulation to the central nervous system. Front Neurosci, 11:617.

[75]Modica S, Murzilli S, Salvatore L, et al., 2008. Nuclear bile acid receptor FXR protects against intestinal tumorigenesis. Cancer Res, 68(23):9589-9594.

[76]Mullish BH, Forlano R, Manousou P, et al., 2018. Non-alcoholic fatty liver disease and cardiovascular risk: an update. Expert Rev Gastroenterol Hepatol, 12(12):1175-1177.

[77]Nakatani H, Kasama K, Oshiro T, et al., 2009. Serum bile acid along with plasma incretins and serum high-molecular weight adiponectin levels are increased after bariatric surgery. Metabolism, 58(10):1400-1407.

[78]Natividad JM, Lamas B, Pham HP, et al., 2018. Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice. Nat Commun, 9(1):2802.

[79]Nguyen TT, Ung TT, Kim NH, et al., 2018. Role of bile acids in colon carcinogenesis. World J Clin Cases, 6(13):577-588.

[80]https://doi.org/10.12998/wjcc.v6.i13.577

[81]Nho K, Kueider-Paisley A, Mahmoudiandehkordi S, et al., 2019. Altered bile acid profile in mild cognitive impairment and Alzheimer’s disease: relationship to neuroimaging and CSF biomarkers. Alzheimers Dement, 15(2):232-244.

[82]Panek-Jeziorna M, Mulak A, 2017. The role of bile acids in the pathogenesis of bowel diseases. Postepy Hig Med Dosw (Online), 71(1):737-746.

[83]Pathak P, Liu HL, Boehme S, et al., 2017. Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism. J Biol Chem, 292(26):11055-11069.

[84]Patti ME, Houten SM, Bianco AC, et al., 2009. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring), 17(9):1671-1677.

[85]Prinz P, Hofmann T, Ahnis A, et al., 2015. Plasma bile acids show a positive correlation with body mass index and are negatively associated with cognitive restraint of eating in obese patients. Front Neurosci, 9:199.

[86]Puri P, Daita K, Joyce A, et al., 2018. The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids. Hepatology, 67(2):534-548.

[87]Richter HGF, Benson GM, Blum D, et al., 2011. Discovery of novel and orally active FXR agonists for the potential treatment of dyslipidemia & diabetes. Bioorg Med Chem Lett, 21(1):191-194.

[88]Ridaura VK, Faith JJ, Rey FE, et al., 2013. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 341(6150):1241214.

[89]Ridlon JM, Kang DJ, Hylemon PB, 2006. Bile salt biotransformations by human intestinal bacteria. J Lipid Res, 47(2):241-259.

[90]Ryan KK, Tremaroli V, Clemmensen C, et al., 2014. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature, 509(7499):183-188.

[91]Sandoval DA, 2019. Mechanisms for the metabolic success of bariatric surgery. J Neuroendocrinol, e12708.

[92]Sato H, Genet C, Strehle A, et al., 2007. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun, 362(4):793-798.

[93]Schmid A, Neumann H, Karrasch T, et al., 2016. Bile acid metabolome after an oral lipid tolerance test by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PLoS ONE, 11(2):e0148869.

[94]Schmid A, Schlegel J, Thomalla M, et al., 2019. Evidence of functional bile acid signaling pathways in adipocytes. Mol Cell Endocrinol, 483:1-10.

[95]Schwabl P, Hambruch E, Seeland BA, et al., 2017. The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction. J Hepatol, 66(4):724-733.

[96]Shen J, Obin MS, Zhao LP, 2013. The gut microbiota, obesity and insulin resistance. Mol Aspects Med, 34(1):39-58.

[97]Shima KR, Ota T, Kato KI, et al., 2018. Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon-like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: a pilot randomized controlled and add-on study. BMJ Open Diabetes Res Care, 6(1):e000469.

[98]Slijepcevic D, van de Graaf SFJ, 2017. Bile acid uptake transporters as targets for therapy. Dig Dis, 35(3):251-258.

[99]Soderborg TK, Clark SE, Mulligan CE, et al., 2018. The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD. Nat Commun, 9(1):4462.

[100]Sommer A, Twig G, 2018. The impact of childhood and adolescent obesity on cardiovascular risk in adulthood: a systematic review. Curr Diab Rep, 18(10):91.

[101]Sun LL, Xie C, Wang G, et al., 2018. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med, 24(12):1919-1929.

[102]Tang WHW, Li DY, Hazen SL, 2019. Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol, 16(3):137-154.

[103]Thompson MD, Moghe A, Cornuet P, et al., 2018. β-Catenin regulation of farnesoid X receptor signaling and bile acid metabolism during murine cholestasis. Hepatology, 67(3):955-971.

[104]Tian JY, Huang S, Sun SM, et al., 2017. Bile acid signaling and bariatric surgery. Liver Res, 1(4):208-213.

[105]Tiratterra E, Franco P, Porru E, et al., 2018. Role of bile acids in inflammatory bowel disease. Ann Gastroenterol, 31(3):266-272.

[106]https://doi.org/10.20524/aog.2018.0239

[107]Trauner M, Gulamhusein A, Hameed B, et al., 2019. The nonsteroidal farnesoid X receptor agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with primary sclerosing cholangitis. Hepatology, Epub ahead of print.

[108]Tsuchiya T, Naitoh T, Nagao M, et al., 2018. Increased bile acid signals after duodenal-jejunal bypass improve non-alcoholic steatohepatitis (NASH) in a rodent model of diet-induced NASH. Obes Surg, 28(6):1643-1652.

[109]Turnbaugh PJ, Ley RE, Mahowald MA, et al., 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122):1027-1031.

[110]Velazquez-Villegas LA, Perino A, Lemos V, et al., 2018. TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue. Nat Commun, 9:245.

[111]Verbeke L, Farre R, Trebicka J, et al., 2014. Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats. Hepatology, 59(6):2286-2298.

[112]Wang J, Greene S, Eriksson LC, et al., 2005. Human sterol 12α-hydroxylase (CYP8B1) is mainly expressed in hepatocytes in a homogenous pattern. Histochem Cell Biol, 123(4-5):441-446.

[113]Wang J, Olin M, Rozell B, et al., 2007. Differential hepatocellular zonation pattern of cholesterol 7α-hydroxylase (Cyp7a1) and sterol 12α-hydroxylase (Cyp8b1) in the mouse. Histochem Cell Biol, 127(3):253-261.

[114]Wang K, Liao MF, Zhou N, et al., 2019. Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids. Cell Rep, 26(1):222-235.e5.

[115]Wang MG, Wu QZ, Xie HB, et al., 2017. Effects of sleeve gastrectomy on serum 12α-hydroxylated bile acids in a diabetic rat model. Obes Surg, 27(11):2912-2918.

[116]Wang XC, Fu XH, van Ness C, et al., 2013. Bile acid receptors and liver cancer. Curr Pathobiol Rep, 1(1):29-35.

[117]Wang YD, Chen WD, Wang MH, et al., 2008. Farnesoid X receptor antagonizes nuclear factor κB in hepatic inflammatory response. Hepatology, 48(5):1632-1643.

[118]Watanabe K, Ohta M, Takayama H, et al., 2018. Effects of sleeve gastrectomy on nonalcoholic fatty liver disease in an obese rat model. Obes Surg, 28(6):1532-1539.

[119]Watanabe M, Houten SM, Mataki C, et al., 2006. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature, 439(7075):484-489.

[120]Wei YJ, Lu Y, Zhu YL, et al., 2018. Structural basis for the hepatoprotective effects of antihypertensive 1,4-dihydropyridine drugs. Biochim Biophys Acta Gen Subj, 1862(10):2261-2270.

[121]Worthmann A, John C, Rühlemann MC, et al., 2017. Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis. Nat Med, 23(7):839-849.

[122]Xu YXZ, Mishra S, 2018. Obesity-linked cancers: current knowledge, challenges and limitations in mechanistic studies and rodent models. Cancers, 10(12):523.

[123]Yang F, Huang XF, Yi TS, et al., 2007. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res, 67(3):863-867.

[124]Yang ZY, Li J, Xiong FX, et al., 2016. Berberine attenuates high glucose-induced fibrosis by activating the G protein-coupled bile acid receptor TGR5 and repressing the S1P2/MAPK signaling pathway in glomerular mesangial cells. Exp Cell Res, 346(2):241-247.

[125]Yoneno K, Hisamatsu T, Shimamura K, et al., 2013. TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn’s disease. Immunology, 139(1):19-29.

[126]Zaborska KE, Cummings BP, 2018. Rethinking bile acid metabolism and signaling for type 2 diabetes treatment. Curr Diab Rep, 18(11):109.

[127]Zhao SN, Gong ZZ, Zhou JF, et al., 2016. Deoxycholic acid triggers NLRP3 inflammasome activation and aggravates DSS-induced colitis in mice. Front Immunol, 7:536.

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