Volume 12 Issue 5
May  2021
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Wei Jia, Meilin Wei, Cynthia Rajani, Xiaojiao Zheng. Targeting the alternative bile acid synthetic pathway for metabolic diseases[J]. Protein&Cell, 2021, 12(5): 411-425. doi: 10.1007/s13238-020-00804-9
Citation: Wei Jia, Meilin Wei, Cynthia Rajani, Xiaojiao Zheng. Targeting the alternative bile acid synthetic pathway for metabolic diseases[J]. Protein&Cell, 2021, 12(5): 411-425. doi: 10.1007/s13238-020-00804-9

Targeting the alternative bile acid synthetic pathway for metabolic diseases

doi: 10.1007/s13238-020-00804-9
  • Received Date: 2020-07-07
  • Rev Recd Date: 2020-10-21
  • The gut microbiota is profoundly involved in glucose and lipid metabolism, in part by regulating bile acid (BA) metabolism and affecting multiple BA-receptor signaling pathways. BAs are synthesized in the liver by multi-step reactions catalyzed via two distinct routes, the classical pathway (producing the 12α-hydroxylated primary BA, cholic acid), and the alternative pathway (producing the non-12α-hydroxylated primary BA, chenodeoxycholic acid). BA synthesis and excretion is a major pathway of cholesterol and lipid catabolism, and thus, is implicated in a variety of metabolic diseases including obesity, insulin resistance, and nonalcoholic fatty liver disease. Additionally, both oxysterols and BAs function as signaling molecules that activate multiple nuclear and membrane receptor-mediated signaling pathways in various tissues, regulating glucose, lipid homeostasis, inflammation, and energy expenditure. Modulating BA synthesis and composition to regulate BA signaling is an interesting and novel direction for developing therapies for metabolic disease. In this review, we summarize the most recent findings on the role of BA synthetic pathways, with a focus on the role of the alternative pathway, which has been under-investigated, in treating hyperglycemia and fatty liver disease. We also discuss future perspectives to develop promising pharmacological strategies targeting the alternative BA synthetic pathway for the treatment of metabolic diseases.
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    Kaur A, Patankar JV, de Haan W, Ruddle P, Wijesekara N, Groen AK, Verchere CB, Singaraja RR, Hayden MR (2015) Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1. Diabetes 64:1168-1179
    Arora T, Bäckhed F (2016) The gut microbiota and metabolic disease:current understanding and future perspectives. J Intern Med 280:339-349
    Bai Q, Zhang X, Xu L, Kakiyama G, Heuman D, Sanyal A, Pandak WM, Yin L, Xie W, Ren S (2012) Oxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor/sterol regulatory element binding protein-1c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver disease. Metabolism 61:836-845
    Baranowski M, Zabielski P, Blachnio-Zabielska AU, Harasim E, Chabowski A, Gorski J (2014) Insulin-sensitizing effect of LXR agonist T0901317 in high-fat fed rats is associated with restored muscle GLUT4 expression and insulin-stimulated AS160 phosphorylation. Cell Physiol Biochem 33:1047-1057
    Bennett MJ, McKnight SL, Coleman JP (2003) Cloning and characterization of the NAD-dependent 7α-hydroxysteroid dehydrogenase from Bacteroides fragilis. Curr Microbiol 47:475-484
    Benoit B, Meugnier E, Castelli M, Chanon S, Vieille-Marchiset A, Durand C, Bendridi N, Pesenti S, Monternier PA, Durieux AC et al (2017) Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice. Nat Med 23:990-996
    Bertaggia E, Jensen KK, Castro-Perez J, Xu Y, Di Paolo G, Chan RB, Wang L, Haeusler RA (2017) Ablation prevents Western diet-induced weight gain and hepatic steatosis because of impaired fat absorption. Am J Physiol Endocrinol Metab 313:E121-E133
    Biddinger SB, Haas JT, Yu BB, Bezy O, Jing E, Zhang W, Unterman TG, Carey MC, Kahn CR (2008) Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med 14:778-782
    Bovenga F, Sabba C, Moschetta A (2015) Uncoupling nuclear receptor LXR and cholesterol metabolism in cancer. Cell Metab 21:517-526
    Brown AJ, Jessup W (2009) Oxysterols:sources, cellular storage and metabolism, and new insights into their roles in cholesterol homeostasis. Mol Asp Med 30:111-122
    Brufau G, Stellaard F, Prado K, Bloks VW, Jonkers E, Boverhof R, Kuipers F, Murphy EJ (2010) Improved glycemic control with colesevelam treatment in patients with type 2 diabetes is not directly associated with changes in bile acid metabolism. Hepatology (Baltim Md) 52:1455-1464
    Caballero F, Fernandez A, De Lacy AM, Fernandez-Checa JC, Caballeria J, Garcia-Ruiz C (2009) Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. J Hepatol 50:789-796
    Chang CC, Sakashita N, Ornvold K, Lee O, Chang ET, Dong R, Lin S, Lee CY, Strom SC, Kashyap R et al (2000) Immunological quantitation and localization of ACAT-1 and ACAT-2 in human liver and small intestine. J Biol Chem 275:28083-28092
    Chang TY, Li BL, Chang CC, Urano Y (2009) Acyl-coenzyme A:cholesterol acyltransferases. Am J Physiol Endocrinol Metab 297:E1-E9
    Chen C, Hu B, Wu T, Zhang Y, Xu Y, Feng Y, Jiang H (2016) Bile acid profiles in diabetic (db/db) mice and their wild type littermates. J Pharm Biomed Anal 131:473-481
    Clare K, Hardwick SJ, Carpenter KL, Weeratunge N, Mitchinson MJ (1995) Toxicity of oxysterols to human monocyte-macrophages. Atherosclerosis 118:67-75
    de Aguiar Vallim TQ, Tarling EJ, Edwards PA (2013) Pleiotropic roles of bile acids in metabolism. Cell Metab 17:657-669
    Degirolamo C, Sabba C, Moschetta A (2016) Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. Nat Rev Drug Discov 15:51-69
    Dong Z, Lee BH (2018) Bile salt hydrolases:structure and function, substrate preference, and inhibitor development. Protein Sci 27:1742-1754
    Edenharder R, Pfützner M, Hammann R (1989) NADP-dependent 3 beta-, 7 alpha- and 7 beta-hydroxysteroid dehydrogenase activities from a lecithinase-lipase-negative Clostridium species 25.11.c. Biochim Biophys Acta 1002:37-44
    Broeders EP, Nascimento EB, Havekes B, Brans B, Roumans KH, Tailleux A, Schaart G, Kouach M, Charton J, Deprez B et al (2015) The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab 22:418-426
    Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y et al (2015) Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med 21:159-165
    Schaap FG, Trauner M, Jansen PLM (2014) Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol 11:55-67
    Fu L, John LM, Adams SH, Yu XX, Tomlinson E, Renz M, Williams PM, Soriano R, Corpuz R, Moffat B et al (2004) Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology 145:2594-2603
    Geenes V, Lovgren-Sandblom A, Benthin L, Lawrance D, Chambers J, Gurung V, Thornton J, Chappell L, Khan E, Dixon P et al (2014) The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid. PLoS ONE 9:e83828
    Goessling W, North TE (2016) EnaBILEing growth in the fetal liver. Cell Stem Cell 18:427-428
    Guillemot-Legris O, Mutemberezi V, Muccioli GG (2016) Oxysterols in metabolic syndrome:from bystander molecules to bioactive lipids. Trends Mol Med 22:594-614
    Han J, Qin WX, Li ZL, Xu AJ, Xing H, Wu H, Zhang H, Wang MD, Li C, Liang L et al (2019) Tissue and serum metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma. Clin Chim Acta 488:68-75
    Higuchi N, Kato M, Shundo Y, Tajiri H, Tanaka M, Yamashita N, Kohjima M, Kotoh K, Nakamuta M, Takayanagi R et al (2008) Liver X receptor in cooperation with SREBP-1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease. Hepatol Res 38:1122-1129
    Huang F, Zheng X, Ma X, Jiang R, Zhou W, Zhou S, Zhang Y, Lei S, Wang S, Kuang J et al (2019) Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism. Nat Commun 10:4971
    Ikegami T, Hyogo H, Honda A, Miyazaki T, Tokushige K, Hashimoto E, Inui K, Matsuzaki Y, Tazuma S (2012) Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease. J Gastroenterol 47:1257-1266
    Itoh S, Onishi S (2000) Hepatic taurine, glycine and individual bile acids in early human fetus. Early Hum Dev 57:71-77
    Jia W, Xie G, Jia W (2018) Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol 15:111-128
    Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S (2012) Host-gut microbiota metabolic interactions. Science 336:1262-1267
    Kakiyama G, Marques D, Takei H, Nittono H, Erickson S, Fuchs M, Rodriguez-Agudo D, Gil G, Hylemon PB, Zhou H et al (2019) Mitochondrial oxysterol biosynthetic pathway gives evidence for CYP7B1 as controller of regulatory oxysterols. J Steroid Biochem Mol Biol 189:36-47
    Kim I, Ahn S-H, Inagaki T, Choi M, Ito S, Guo GL, Kliewer SA, Gonzalez FJ (2007) Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J Lipid Res 48:2664-2672
    Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S, Joseph SB, Castrillo A, Wilpitz DC, Mangelsdorf DJ, Collins JL et al (2003) Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc Natl Acad Sci USA 100:5419-5424
    Lake AD, Novak P, Shipkova P, Aranibar N, Robertson D, Reily MD, Lu Z, Lehman-McKeeman LD, Cherrington NJ (2013) Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease. Toxicol Appl Pharmacol 268:132-140
    Laurin J, Lindor KD, Crippin JS, Gossard A, Gores GJ, Ludwig J, Rakela J, McGill DB (1996) Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis:a pilot study. Hepatology 23:1464-1467
    Li C, Yang W, Zhang J, Zheng X, Yao Y, Tu K, Liu Q (2014) SREBP-1 has a prognostic role and contributes to invasion and metastasis in human hepatocellular carcinoma. Int J Mol Sci 15:7124-7138
    Li J, Zheng X, Lou N, Zhong W, Yan D (2016) Oxysterol binding protein-related protein 8 mediates the cytotoxicity of 25-hydroxycholesterol. J Lipid Res 57:1845-1853
    Li P, Ruan X, Yang L, Kiesewetter K, Zhao Y, Luo H, Chen Y, Gucek M, Zhu J, Cao H (2015) A liver-enriched long non-coding RNA, lncLSTR, regulates systemic lipid metabolism in mice. Cell Metab 21:455-467
    Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, Lymp JF, Burgart L, Colin P (2004) Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis:results of a randomized trial. Hepatology (Baltim Md) 39:770-778
    Liu N, Feng J, Lv Y, Liu Q, Deng J, Xia Y, Guo C, Zhou Y (2019) Role of bile acids in the diagnosis and progression of liver cirrhosis:a prospective observational study. Exp Ther Med 18:4058-4066
    Lofthouse EM, Torrens C, Manousopoulou A, Nahar M, Cleal JK, O'Kelly IM, Sengers BG, Garbis SD, Lewis RM (2019) Ursodeoxycholic acid inhibits uptake and vasoconstrictor effects of taurocholate in human placenta. FASEB J 33:8211-8220
    Long H, Guo X, Qiao S, Huang Q (2018) Tumor LXR expression is a prognostic marker for patients with hepatocellular carcinoma. Pathol Oncol Res 24:339-344
    Lu M, Hu XH, Li Q, Xiong Y, Hu GJ, Xu JJ, Zhao XN, Wei XX, Chang CC, Liu YK et al (2013) A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth. J Mol Cell Biol 5:404-415
    Ma H, Sales VM, Wolf AR, Subramanian S, Matthews TJ, Chen M, Sharma A, Gall W, Kulik W, Cohen DE et al (2017) Attenuated effects of bile acids on glucose metabolism and insulin sensitivity in a male mouse model of prenatal undernutrition. Endocrinology 158:2441-2452
    Macdonald IA, Hutchison DM, Forrest TP, Bokkenheuser VD, Winter J, Holdeman LV (1983) Metabolism of primary bile acids by Clostridium perfringens. J Steroid Chem 18:97-104
    Matsuoka K, Suzuki M, Honda C, Endo K, Moroi Y (2006) Micellization of conjugated chenodeoxy- and ursodeoxycholates and solubilization of cholesterol into their micelles:comparison with other four conjugated bile salts species. Chem Phys Lipids 139:1-10
    Min HK, Kapoor A, Fuchs M, Mirshahi F, Zhou H, Maher J, Kellum J, Warnick R, Contos MJ, Sanyal AJ (2012) Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab 15:665-674
    Miura S, Mitsuhashi N, Shimizu H, Kimura F, Yoshidome H, Otsuka M, Kato A, Shida T, Okamura D, Miyazaki M (2012) Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma. BMC Cancer 12:56
    Monte MJ, Marin JJ, Antelo A, Vazquez-Tato J (2009) Bile acids:chemistry, physiology, and pathophysiology. World J Gastroenterol 15:804
    Mueller M, Thorell A, Claudel T, Jha P, Koefeler H, Lackner C, Hoesel B, Fauler G, Stojakovic T, Einarsson C (2015) Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. J Hepatol 62:1398-1404
    Mulder TPJ, van Platerink CJ, Schuyl PJW, van Amelsvoort JMM (2001) Analysis of theaflavins in biological fluids using liquid chromatography-electrospray mass spectrometry. J Chromatogr B 760:271-279
    Mutemberezi V, Guillemot-Legris O, Muccioli GG (2016) Oxysterols:from cholesterol metabolites to key mediators. Prog Lipid Res 64:152-169
    Na TY, Shin YK, Roh KJ, Kang SA, Hong I, Oh SJ, Seong JK, Park CK, Choi YL, Lee MO (2009) Liver X receptor mediates hepatitis B virus X protein-induced lipogenesis in hepatitis B virus-associated hepatocellular carcinoma. Hepatology 49:1122-1131
    Nakagawa M, Setchell KD (1990) Bile acid metabolism in early life:studies of amniotic fluid. J Lipid Res 31:1089-1098
    Nojima K, Sugimoto K, Ueda H, Babaya N, Ikegami H, Rakugi H (2013) Analysis of hepatic gene expression profile in a spontaneous mouse model of type 2 diabetes under a high sucrose diet. Endocr J 60:261-274
    Chávez-Talavéra O, Tailleux A, Lefebvre P, Staels B (2017) Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology 152:1679-1694.e1673
    Oram JF, Heinecke JW (2005) ATP-binding cassette transporter A1:a cell cholesterol exporter that protects against cardiovascular disease. Physiol Rev 85:1343-1372
    Pai R, Dunlap D, Qing J, Mohtashemi I, Hotzel K, French DM (2008) Inhibition of fibroblast growth factor 19 reduces tumor growth by modulating beta-catenin signaling. Cancer Res 68:5086-5095
    Pandak WM, Kakiyama G (2019) The acidic pathway of bile acid synthesis:not just an alternative pathway. Liver Res 3:88-98
    Pannu PS, Allahverdian S, Francis GA (2013) Oxysterol generation and liver X receptor-dependent reverse cholesterol transport:not all roads lead to Rome. Mol Cell Endocrinol 368:99-107
    Pathak P, Chiang JY (2019) Sterol 12α-hydroxylase aggravates dyslipidemia by activating the ceramide/mTORC1/SREBP-1C pathway via FGF21 and FGF15. Gene Expr J Liver Res 19:161-173
    Piglionica M, Cariello M, Moschetta A (2018) The gut-liver axis in hepatocarcinoma:a focus on the nuclear receptor FXR and the enterokine FGF19. Curr Opin Pharmacol 43:93-98
    Haeusler RA, Astiarraga B, Camastra S, Accili D, Ferrannini E (2013) Human insulin resistance is associated with increased plasma levels of 12α-hydroxylated bile acids. Diabetes 62:4184-4191
    Raccosta L, Fontana R, Corna G, Maggioni D, Moresco M, Russo V (2016) Cholesterol metabolites and tumor microenvironment:the road towards clinical translation. Cancer Immunol Immunother 65:111-117
    Raccosta L, Fontana R, Maggioni D, Lanterna C, Villablanca EJ, Paniccia A, Musumeci A, Chiricozzi E, Trincavelli ML, Daniele S et al (2013) The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils. J Exp Med 210:1711-1728
    Rao A, Kosters A, Mells JE, Zhang W, Setchell KD, Amanso AM, Wynn GM, Xu T, Keller BT, Yin H (2016) Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice. Sci Transl Med 8:357ra122
    Ren S, Li X, Rodriguez-Agudo D, Gil G, Hylemon P, Pandak WM (2007) Sulfated oxysterol, 25HC3S, is a potent regulator of lipid metabolism in human hepatocytes. Biochem Biophys Res Commun 360:802-808
    Ridlon JM, Kang D-J, Hylemon PB (2006) Bile salt biotransformations by human intestinal bacteria. J Lipid Res 47:241-259
    Roma MG, Toledo FD, Boaglio AC, Basiglio CL, Crocenzi FA, Sanchez Pozzi EJ (2011) Ursodeoxycholic acid in cholestasis:linking action mechanisms to therapeutic applications. Clin Sci (Lond) 121:523-544
    Sayin SI, Wahlstrom A, Felin J, Jantti S, Marschall HU, Bamberg K, Angelin B, Hyotylainen T, Oresic M, Backhed F (2013) Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 17:225-235
    Seo KH, Bartley GE, Tam C, Kim HS, Kim DH, Chon JW, Kim H, Yokoyama W (2016) Chardonnay grape seed flour ameliorates hepatic steatosis and insulin resistance via altered hepatic gene expression for oxidative stress, inflammation, and lipid and ceramide synthesis in diet-induced obese mice. PLoS ONE 11:e0167680
    Setchell KD, Dumaswala R, Colombo C, Ronchi M (1988) Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. J Biol Chem 263:16637-16644
    Sigurdsson V, Takei H, Soboleva S, Radulovic V, Galeev R, Siva K, Leeb-Lundberg LM, Iida T, Nittono H, Miharada K (2016) Bile acids protect expanding hematopoietic stem cells from unfolded protein stress in fetal liver. Cell Stem Cell 18:522-532
    Smith K, Zeng X, Lin J (2014) Discovery of bile salt hydrolase inhibitors using an efficient high-throughput screening system. PLoS ONE 9:e85344
    Spencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA (2011) Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology 140:976-986
    Su GL (2002) Lipopolysaccharides in liver injury:molecular mechanisms of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol 283:G256-G265
    Su K, Sabeva NS, Liu J, Wang Y, Bhatnagar S, van der Westhuyzen DR, Graf GA (2012) The ABCG5 ABCG8 sterol transporter opposes the development of fatty liver disease and loss of glycemic control independently of phytosterol accumulation. J Biol Chem 287:28564-28575
    Takeyama Y, Uehara Y, Anan A, Morihara D, Yokoyama K, Takata K, Tanaka T, Irie M, Iwata K, Shakado S et al (2017) Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients. Med Mol Morphol 50:227-237
    Tang R, Wei Y, Li Y, Chen W, Chen H, Wang Q, Yang F, Miao Q, Xiao X, Zhang H (2018) Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy. Gut 67:534-541
    Trabelsi MS, Daoudi M, Prawitt J, Ducastel S, Touche V, Sayin SI, Perino A, Brighton CA, Sebti Y, Kluza J et al (2015) Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat Commun 6:7629
    Massafra V, Pellicciari R, Gioiello A, van Mil SWC (2018) Progress and challenges of selective Farnesoid X Receptor modulation. Pharmacol Ther 191:162-177
    Vaz FM, Ferdinandusse S (2017) Bile acid analysis in human disorders of bile acid biosynthesis. Mol Asp Med 56:10-24
    Villablanca EJ, Raccosta L, Zhou D, Fontana R, Maggioni D, Negro A, Sanvito F, Ponzoni M, Valentinis B, Bregni M et al (2010) Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7 expression on dendritic cells and dampens antitumor responses. Nat Med 16:98-105
    Wahlström A, Sayin SI, Marschall H-U, Bäckhed F (2016) Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab 24:41-50
    Wang DQ, Tazuma S, Cohen DE, Carey MC (2003) Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption:studies in the gallstone-susceptible mouse. Am J Physiol Gastrointest Liver Physiol 285:G494-G502
    Wei M, Huang F, Zhao L, Zhang Y, Yang W, Wang S, Li M, Han X, Ge K, Qu C et al (2020) A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility. EBioMedicine 55:102766
    Wikstrom Shemer E, Marschall HU, Ludvigsson JF, Stephansson O (2013) Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes:a 12-year population-based cohort study. BJOG 120:717-723
    Worthmann A, John C, Rühlemann MC, Baguhl M, Heinsen F-A, Schaltenberg N, Heine M, Schlein C, Evangelakos I, Mineo C et al (2017) Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis. Nat Med 23:839-849
    Xu L, Kim JK, Bai Q, Zhang X, Kakiyama G, Min HK, Sanyal AJ, Pandak WM, Ren S (2013) 5-Cholesten-3beta, 25-diol 3-sulfate decreases lipid accumulation in diet-induced nonalcoholic fatty liver disease mouse model. Mol Pharmacol 83:648-658
    Xu L, Shen S, Ma Y, Kim JK, Rodriguez-Agudo D, Heuman DM, Hylemon PB, Pandak WM, Ren S (2012) 25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPARgamma signaling in human THP-1 macrophages. Am J Physiol Endocrinol Metab 302:E788-799
    Yang Y, Jiang Y, Wang Y, An W (2010) Suppression of ABCA1 by unsaturated fatty acids leads to lipid accumulation in HepG2 cells. Biochimie 92:958-963
    Yokota A, Fukiya S, Islam KS, Ooka T, Ogura Y, Hayashi T, Hagio M, Ishizuka S (2012) Is bile acid a determinant of the gut microbiota on a high-fat diet? Gut Microbes 3:455-459
    Yu H, Ni Y, Bao Y, Zhang P, Zhao A, Chen T, Xie G, Tu Y, Zhang L, Su M et al (2015) Chenodeoxycholic acid as a potential prognostic marker for Roux-en-Y gastric bypass in Chinese obese patients. J Clin Endocrinol Metab 100:4222-4230
    Zhang Y, Jiang R, Zheng X, Lei S, Huang F, Xie G, Kwee S, Yu H, Farrar C, Sun B et al (2019) Ursodeoxycholic acid accelerates bile acid enterohepatic circulation. Br J Pharmacol 176:2848-2863
    Zhang Y, Pan Y, Lin C, Zheng Y, Sun H, Zhang H, Wang J, Yuan M, Duan T, Du Q et al (2016) Bile acids evoke placental inflammation by activating Gpbar1/NF-kappaB pathway in intrahepatic cholestasis of pregnancy. J Mol Cell Biol 8:530-541
    Zhong W, Qin S, Zhu B, Pu M, Liu F, Wang L, Ye G, Yi Q, Yan D (2015) Oxysterol-binding protein-related protein 8 (ORP8) increases sensitivity of hepatocellular carcinoma cells to Fas-mediated apoptosis. J Biol Chem 290:8876-8887
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