Non alcoholic steatohepatitis a precursor for hepatocellular carcinoma development

World Journal of Gastroenterology

Volumn 20, Issue 44, 2014, Pages 16464-16473

  Jiang, Chun Meng ^a   Pu, Chun Wen ^b   Hou, Ya Hui ^a   Chen, Zhe ^a   Alanazy, Mohammed ^c   Hebbard, Lionel ^c  

^a DALIAN MEDICAL UNIVERSITY   (China)

^b Dalian Sixth People's Hospital   (China)

^c UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Bile acids; Hepatocellular carcinoma; Inflammation; Microbiome; Nonalcoholic steatohepatitis

Indexed keywords

ADIPONECTIN; BILE ACID; CYTOKINE; INTERLEUKIN 6; LEPTIN; TUMOR NECROSIS FACTOR ALPHA;

ADIPOSE TISSUE; ARTICLE; CANCER GROWTH; CANCER RISK; CELL FUNCTION; CELL RESPIRATION; DYSBIOSIS; ENERGY METABOLISM; HEPATITIS; HUMAN; IN VIVO STUDY; INFLAMMATION; INSULIN RELEASE; INTESTINE; INTESTINE FLORA; LIPID DIET; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FIBROSIS; LIVER METABOLISM; MICROBIOME; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; STEATOSIS; STELLATE CELL; TUMOR CELL;

EID: 84964313873     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i44.16464     Document Type: Article

References (93)

1. Cabibbo G, Craxî A. Epidemiology, risk factors and surveillance of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci 2010; 14: 352-355 [PMID: 20496547]
2. Brunt EM. Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2010; 7: 195-203 [PMID: 20195271 DOI: 10.1038/nrgastro.2010.21]
3. Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol 2013; 28 Suppl 1: 68-76 [PMID: 23855299]
4. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology 1998; 114: 842-845 [PMID: 9547102]
5. Gastaldelli A, Harrison S, Belfort-Aguiar R, Hardies J, Balas B, Schenker S, Cusi K. Pioglitazone in the treatment of NASH: the role of adiponectin. Aliment Pharmacol Ther 2010; 32: 769-775 [PMID: 20662773]
6. Kugelmas M, Hill DB, Vivian B, Marsano L, McClain CJ. Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 2003; 38: 413-419 [PMID: 12883485]
7. Koek GH, Liedorp PR, Bast A. The role of oxidative stress in non-alcoholic steatohepatitis. Clin Chim Acta 2011; 412: 1297-1305 [PMID: 21514287 DOI: 10.1016/j.cca.2011.04.013]
8. Loria P, Carulli L, Bertolotti M, Lonardo A. Endocrine and liver interaction: the role of endocrine pathways in NASH. Nat Rev Gastroenterol Hepatol 2009; 6: 236-247 [PMID: 19347015 DOI: 10.1038/nrgastro.2009.33]
9. Michelotti G A, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol 2013; 10: 656-665 [PMID: 24080776 DOI: 10.1038/nrgastro.2013.183]
10. Yu J, Shen J, Sun TT, Zhang X, Wong N. Obesity, insulin resistance, NASH and hepatocellular carcinoma. Semin Cancer Biol 2013; 23: 483-491 [PMID: 23876851 DOI: 10.1016/ j.semcancer.2013.07.003]
11. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129:113-121 [PMID: 16012941]
12. Jansen PL. Non-alcoholic steatohepatitis. Eur J Gastroenterol Hepatol 2004; 16: 1079-1085 [PMID: 15489564]
13. Nagaoki Y, Hyogo H, Aikata H, Tanaka M, Naeshiro N, Nakahara T, Honda Y, Miyaki D, Kawaoka T, Takaki S, Hiramatsu A, Waki K, Imamura M, Kawakami Y, Takahashi S, Chayama K. Recent trend of clinical features in patients with hepatocellular carcinoma. Hepatol Res 2012; 42: 368-375 [PMID: 22151896 DOI: 10.1111/j.1872-034X.2011.00929.x]
14. Hashimoto E, Yatsuji S, Tobari M, Taniai M, Torii N, Tokushige K, Shiratori K. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol 2009; 44 Suppl 19: 89-95 [PMID: 19148800 DOI: 10.1007/s00535-008-2262-x]
15. Sanyal A, Poklepovic A, Moyneur E, Barghout V. Population-based risk factors and resource utilization for HCC: US perspective. Curr Med Res Opin 2010; 26: 2183-2191 [PMID: 20666689 DOI: 10.1185/03007995.2010.506375]
16. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 2010; 51: 1820-1832 [PMID: 20432259 DOI: 10.1002/hep.23594]
17. Kawada N, Imanaka K, Kawaguchi T, Tamai C, Ishihara R, Matsunaga T, Gotoh K, Yamada T, Tomita Y. Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis. J Gastroenterol 2009; 44: 1190-1194 [PMID: 19672551 DOI: 10.1007/s00535-009-0112-0]
18. Karagozian R, Derdák Z, Baffy G. Obesity-associated mechanisms of hepatocarcinogenesis. Metabolism 2014; 63: 607-617 [PMID: 24629562 DOI: 10.1016/j.metabol.2014.01.011]
19. Schett G, Elewaut D, Mclnnes IB, Dayer JM, Neurath MF. How cytokine networks fuel inflammation: Toward a cytokine-based disease taxonomy. Nat Med 2013; 19: 822-824 [PMID: 23836224 DOI: 10.1038/nm.3260]
20. Maddur MS, Miossec P, Kaveri SV, Bayry J. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol 2012; 181: 8-18 [PMID: 22640807 DOI: 10.1016/j.ajpath.2012.03.044]
21. Grivennikov SI, Karin M. Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis 2011; 70 Suppl 1: 1104-1108 [PMID: 21339211 DOI: 10.1136/ard.2010.140145]
22. Fukata M, Abreu MT. Role of Toll-like receptors in gastrointestinal malignancies. Oncogene 2008; 27: 234-243 [PMID: 18176605 DOI: 10.1038/sj.onc.1210908]
23. Berasain C, Castillo J, Perugorria MJ, Latasa MU, Prieto J, Avila MA. Inflammation and liver cancer: new molecular links. Ann N Y Acad Sci 2009; 1155: 206-221 [PMID: 19250206 DOI: 10.1111/j.1749-6632.2009.03704.x]
24. He G, Karin M. NF-KB and STAT3 - key players in liver inflammation and cancer. Cell Res 2011; 21: 159-168 [PMID: 21187858 DOI: 10.1038/cr.2010.183]
25. Nakagawa H, Maeda S. Inflammation- and stress-related signaling pathways in hepatocarcinogenesis. World J Gastroenterol 2012; 18: 4071-4081 [PMID: 22919237 DOI: 10.3748/ wjg.v18.131.4071]
26. Maeda S, Kamata H, Luo JL, Leffert H, Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 2005; 121: 977-990 [PMID: 15989949 DOI: 10.1016/ j.cell.2005.04.014]
27. Hirosumi J, Tuncman G, Chang L, Görgün GZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature 2002; 420: 333-336 [PMID: 12447443]
28. Schattenberg JM, Singh R, Wang Y, Lefkowitch JH, Rigoli RM, Scherer PE, Czaja MJ. JNK1 but not JNK2 promotes the development of steatohepatitis in mice. Hepatology 2006; 43: 163-172 [PMID: 16374858]
29. Luedde T, Beraza N, Kotsikoris V, van Loo G, Nenci A, De Vos R, Roskams T, Trautwein G, Pasparakis M. Deletion of NEMO/ IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 2007; 11: 119-132 [PMID: 17292824 DOI: 10.1016/j.ccr.2006.12.016]
30. Siddique A, Kowdley KV. Insulin resistance and other metabolic risk factors in the pathogenesis of hepatocellular carcinoma. Clin Liver Dis 2011; 15: 281-96, vii-x [PMID: 21689613 DOI: 10.1016/j.cld.2011.03.007]
31. He G, Yu GY, Temkin V, Ogata H, Kuntzen C, Sakurai T, Sieghart W, Peck-Radosavljevic M, Leffert HL, Karin M. Hepatocyte IKKbeta/ NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell 2010; 17: 286-297 [PMID: 20227042 DOI: 10.1016/j.ccr.2009.12.048]
32. Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 2008; 103: 1372-1379 [PMID: 18510618 DOI: 10.1111/ j.1572-0241.2007.01774.x]
33. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 2005; 11:183-190 [PMID: 15685173 DOI: 10.1038/nm1166]
34. Maione D, Di Carlo E, Li W, Musiani P, Modesti A, Peters M, Rose-John S, Della Rocca C, Tripodi M, Lazzaro D, Taub R, Savino R, Ciliberto G. Coexpression of IL-6 and soluble IL6R causes nodular regenerative hyperplasia and adenomas of the liver. EMBO J 1998; 17: 5588-5597 [PMID: 9755159 DOI: 10.1093/ emboj/17.19.5588]
35. Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 2007; 317:121-124 [PMID: 17615358 DOI: 10.1126/science.1140485]
36. Naugler WE, Karin M. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med 2008; 14: 109-119 [PMID: 18261959 DOI: 10.1016/ j.molmed.2007.12.007]
37. Elinav E, Ali M, Bruck R, Brazowski E, Phillips A, Shapira Y, Katz M, Solomon G, Halpern Z, Gertler A. Competitive inhibition of leptin signaling results in amelioration of liver fibrosis through modulation of stellate cell function. Hepatology 2009; 49: 278-286 [PMID: 19065677 DOI: 10.1002/ hep.22584]
38. Cao Q, Mak KM, Ren C, Lieber CS. Leptin stimulates tissue inhibitor of metalloproteinase-1 in human hepatic stellate cells: respective roles of the JAK/STAT and JAK-mediated H202-dependant MAPK pathways, J Biol Chem 2004; 279: 4292-4304 [PMID: 14625304 DOI: 10.1074/jbc.M308351200]
39. Cao Q, Mak KM, Lieber CS. Leptin enhances alphal(I) collagen gene expression in LX-2 human hepatic stellate cells through JAK-mediated H202-dependent MAPK pathways. J Cell Biochem 2006; 97: 188-197 [PMID: 16173077 DOI: 10.1002/jcb.20622]
40. Leclercq IA, Farrell GC, Schriemer R, Robertson GR. Leptin is essential for the hepatic fibrogenic response to chronic liver injury, J Hepatol 2002; 37: 206-213 [PMID: 12127425]
41. Chitturi S, Farrell G, Frost L, Kriketos A, Lin R, Fung C, Liddle C, Samarasinghe D, George J. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? Hepatology 2002; 36: 403-409 [PMID: 12143049]
42. Angulo P, Alba LM, Petrovic LM, Adams LA, Lindor KD, Jensen MD. Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease. J Hepatol 2004; 41: 943-949 [PMID: 15582127]
43. Sierra-Honigmann MR, Nath AK, Murakami C, GarciaCardeña G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Flores-Riveros JR. Biological action of leptin as an angiogenic factor. Science 1998; 281: 1683-1686 [PMID: 9733517 DOI: 10.1126/science.281.5383.1683]
44. Kitade M, Yoshiji H, Kojima H, Ikenaka Y, Noguchi R, Kaji K, Yoshii J, Yanase K, Namisaki T, Asada K, Yamazaki M, Tsujimoto T, Akahane T, Uemura M, Fukui H. Leptin-mediated neovascularization is a prerequisite for progression of nonalcoholic steatohepatitis in rats. Hepatology 2006; 44: 983-991 [PMID: 17006938 DOI: 10.1002/hep.21338]
45. Ribatti D, Belloni AS, Nico B, Di Comite M, Crivellato E, Vacca A. Leptin-leptin receptor are involved in angiogenesis in human hepatocellular carcinoma. Peptides 2008; 29: 1596-1602 [PMID: 18573568 DOI: 10.1016/ j.peptides.2008.05.011]
46. Saxena NK, Sharma D, Ding X, Lin S, Marra F, Merlin D, Anania FA. Concomitant activation of the JAK/STAT, PI3K/ AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res 2007; 67: 2497-2507 [PMID: 17363567]
47. Hebbard L, Rauscht B. Multifaceted roles of adiponectin in cancer. Best Pract Res Clin Endocrinol Metab 2014; 28: 59-69 [PMID: 24417946 DOI: 10.1016/j.beem.2013.11.005]
48. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423: 762-769 [PMID: 12802337]
49. Horton JD. Sterol regulatory element-binding proteins: transcriptional activators of lipid synthesis. Biochem Soc Trans 2002; 30:1091-1095 [PMID: 12440980 DOI: 10.1042/]
50. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMPdependent pathway. Circulation 2000; 102: 1296-1301 [PMID: 10982546]
51. Kobashi C, Urakaze M, Kishida M, Kibayashi E, Kobayashi H, Kihara S, Funahashi T, Takata M, Temaru R, Sato A, Yamazaki K, Nakamura N, Kobayashi M. Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res 2005; 97: 1245-1252 [PMID: 16269654 DOI: 10.1161/01. RES.0000194328.57164.36]
52. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000; 96:1723-1732 [PMID: 10961870]
53. Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 2004; 40: 46-54 [PMID: 15239085 DOI: 10.1002/hep.20280]
54. Asano T, Watanabe K, Kubota N, Gunji T, Omata M, Kadowaki T, Ohnishi S. Adiponectin knockout mice on high fat diet develop fibrosing steatohepatitis. J Gastroenterol Hepatol 2009; 24: 1669-1676 [PMID: 19788607 DOI: 10.1111/ j.1440-1746.2009.06039.x]
55. Kamada Y, Tamura S, Kiso S, Matsumoto H, Saji Y, Yoshida Y, Fukui K, Maeda N, Nishizawa H, Nagaretani H, Okamoto Y, Kihara S, Miyagawa J, Shinomura Y, Funahashi T, Matsuzawa Y. Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin. Gastroenterology 2003; 125: 1796-1807 [PMID: 14724832]
56. Zhou M, Xu A, Tam PK, Lam KS, Chan L, Hoo RL, Liu J, Chow KH, Wang Y. Mitochondrial dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injury. Hepatology 2008; 48: 1087-1096 [PMID: 18698578 DOI: 10.1002/hep.22444]
57. Masaki T, Chiba S, Tatsukawa H, Yasuda T, Noguchi H, Seike M, Yoshimatsu H. Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice. Hepatology 2004; 40: 177-184 [PMID: 15239101 DOI: 10.1002/hep.20282]
58. Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003; 112: 91-100 [PMID: 12840063 DOI: 10.1172/ JCI17797112/1/91]
59. Liu CJ, Chen PJ, Lai MY, Liu CH, Chen CL, Kao JH, Chen DS. High serum adiponectin correlates with advanced liver disease in patients with chronic hepatitis B virus infection. Hepatol Int 2009; 3: 364-370 [PMID: 19669362 DOI: 10.1007/ si2072-008-9111-0]
60. Tietge UJ, Böker KH, Manns MP, Bahr MJ. Elevated circulating adiponectin levels in liver cirrhosis are associated with reduced liver function and altered hepatic hemodynamics. Am J Physiol Endocrinol Metab 2004; 287: E82-E89 [PMID: 15010338 DOI: 10.1152/ajpendo.00494.2003]
61. Chen MJ, Yeh YT, Lee KT, Tsai CJ, Lee HH, Wang SN. The promoting effect of adiponectin in hepatocellular carcinoma. J Surg Oncol 2012; 106: 181-187 [PMID: 22287480 DOI: 10.1002/jso.23059]
62. van der Poorten D, Samer CF, Ramezani-Moghadam M, Coulter S, Kacevska M, Schrijnders D, Wu LE, McLeod D, Bugianesi E, Komuta M, Roskams T, Liddle C, Hebbard L, George J. Hepatic fat loss in advanced nonalcoholic steatohepatitis: are alterations in serum adiponectin the cause? Hepatology 2013; 57: 2180-2188 [PMID: 22996622 DOI: 10.1002/hep.26072]
63. Saxena NK, Fu PP, Nagalingam A, Wang J, Handy J, Cohen C, Tighiouart M, Sharma D, Anania FA. Adiponectin modu- lates C-jun N-terminal kinase and mammalian target of rapamycin and inhibits hepatocellular carcinoma. Gastroenterology 2010; 139: 1762-173,1762-173, [PMID: 20637208 DOI: 10.1053/ j.gastro.2010.07.001]
64. Man K, Ng KT, Xu A, Cheng Q, Lo CM, Xiao JW, Sun BS, Lim ZX, Cheung JS, Wu EX, Sun CK, Poon RT, Fan ST. Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/ IFN-inducible protein 10/matrix metalloproteinase 9 signaling. Clin Cancer Res 2010; 16: 967-977 [PMID: 20103676 DOI: 10.1158/1078-0432. CCR-09-1487]
65. Hebbard L, George J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2011; 8: 35-44 [PMID: 21119613 DOI: 10.1038/nrgastro.2010.191]
66. Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut 2001; 48: 206-211 [PMID: 11156641]
67. Shanab AA, Scully P, Crosbie O, Buckley M, O'Mahony L, Shanahan F, Gazareen S, Murphy E, Quigley EM. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8. Dig Dis Sci 2011; 56:1524-1534 [PMID: 21046243 DOI: 10.1007/s10620-010-1447-3]
68. Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, McGilvray ID, Allard JP. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 2013; 58:120-127 [PMID: 23401313 DOI: 10.1002/hep.26319]
69. Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, Gill SR. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 2013; 57: 601-609 [PMID: 23055155 DOI: 10.1002/hep.26093]
70. Velayudham A, Dolganiuc A, Ellis M, Petrasek J, Kodys K, Mandrekar P, Szabo G. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology 2009; 49: 989-997 [PMID: 19115316 DOI: 10.1002/hep.22711]
71. Mencarelli A, Cipriani S, Renga B, Bruno A, D'Amore C, Distrutti E, Fiorucci S. VSL#3 resets insulin signaling and protects against NASH and atherosclerosis in a model of genetic dyslipidemia and intestinal inflammation. PLoS One 2012; 7: e45425 [PMID: 23029000 DOI: 10.1371/journal, pone.0045425]
72. Endo H, Niioka M, Kobayashi N, Tanaka M, Watanabe T. Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: new insight into the probiotics for the gut-liver axis. PLoS One 2013; 8: e63388 [PMID: 23696823 DOI: 10.1371 /journal.pone.0063388]
73. Wong VW, Won GL, Chim AM, Chu WC, Yeung DK, Li KC, Chan HL. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann Hepatol 2013; 12: 256-262 [PMID: 23396737]
74. Malaguarnera M, Vacante M, Antic T, Giordano M, Chisari G, Acquaviva R, Mastrojeni S, Malaguarnera G, Mistretta A, Li Volti G, Galvano F. Bifidobacterium longum with fructooligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci 2012; 57: 545-553 [PMID: 21901256 DOI: 10.1007/ s10620-011-1887-4]
75. Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palù G, Martines D. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2007; 292: G518-G525 [PMID: 17023554 DOI: 10.1152/ajpgi.00024.2006]
76. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57: 1470-1481 [PMID: 18305141 DOI: 10.2337/db07-1403]
77. Imajo K, Fujita K, Yoneda M, Nozaki Y, Ogawa Y, Shinohara Y, Kato S, Mawatari H, Shibata W, Kitani H, Ikejima K, Kirikoshi H, Nakajima N, Saito S, Maeyama S, Watanabe S, Wada K, Nakajima A. Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling. Cell Metab 2012; 16: 44-54 [PMID: 22768838 DOI: 10.1016/j.cmet.2012.05.012]
78. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Thaiss CA, Kau AL, Eisenbarth SC, Jurczak MJ, Camporez JP, Shulman GI, Gordon JI, Hoffman HM, Flavell RA. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012; 482: 179-185 [PMID: 22297845 DOI: 10.1038/naturel0809]
79. Dapito DH, Mencin A, Gwak GY, Pradere JP, Jang MK, Mederacke I, Caviglia JM, Khiabanian H, Adeyemi A, Bataller R, Lefkowitch JH, Bower M, Friedman R, Sartor RB, Rabadan R, Schwabe RF. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012; 21: 504-516 [PMID: 22516259 DOI: 10.1016/j.ccr.2012.02.007]
80. Ridlon JM, Alves JM, Hylemon PB, Bajaj JS. Cirrhosis, bile acids and gut microbiota: unraveling a complex relationship. Gut Microbes 2013; 4: 382-387 [PMID: 23851335 DOI: 10.4161/ gmic.25723]
81. Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, Honda K, Ishikawa Y, Hara E, Ohtani N. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 2013; 499: 97-101 [PMID: 23803760 DOI: 10.1038/naturel2347]
82. Jonker JW, Liddle C, Downes M. FXR and PXR: potential therapeutic targets in cholestasis. J Steroid Biochem Mol Biol 2012; 130: 147-158 [PMID: 21801835 DOI: 10.1016/ j.jsbmb.2011.06.012]
83. Cariou B, van Harmelen K, Duran-Sandoval D, van Dijk TH, Grefhorst A, Abdelkarim M, Caron S, Torpier G, Fruchart JC, Gonzalez FJ, Kuipers F, Staels B. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem 2006; 281: 11039-11049 [PMID: 16446356 DOI: M510258200]
84. Hollman DA, Milona A, van Erpecum KJ, van Mil SW. Antiinflammatory and metabolic actions of FXR: insights into molecular mechanisms. Biochim BiophysActa 2012; 1821:1443-1452 [PMID: 22820415 DOI: 10.1016/j.bbalip.2012.07.004]
85. Zhang S, Wang J, Liu Q, Harnish DC. Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis. J Hepatol 2009; 51: 380-388 [PMID: 19501927 DOI: 10.1016/ j.jhep.2009.03.025]
86. Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU, Kipnes M, Adorini L, Sciacca CI, Clopton P, Castelloe E, Dillon P, Pruzanski M, Shapiro D. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013; 145: 574-82.el [PMID: 23727264 DOI: 10.1053/j.gastro.2013.05.042]
87. Yang F, Huang X, Yi T, Yen Y, Moore DD, Huang W. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res 2007; 67: 863-867 [PMID: 17283114]
88. Wolfe A, Thomas A, Edwards G, Jaseja R, Guo GL, Apte U. Increased activation of the Wnt/β-catenin pathway in spontaneous hepatocellular carcinoma observed in farnesoid X receptor knockout mice. J Pharmacol Exp Ther 2011; 338:12-21 [PMID: 21430080 DOI: 10.1124/jpet.111.179390]
89. Prawitt J, Caron S, Staels B. Bile acid metabolism and the pathogenesis of type 2 diabetes. Curr Diab Rep 2011; 11: 160-166 [PMID: 21431855 DOI: 10.1007/sll892-011-0187-x]
90. Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M, Pellicciari R, Auwerx J, Schoonjans K. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 2009; 10: 167-177 [PMID: 19723493 DOI: 10.1016/j.cmet.2009.08.001]
91. Wang YD, Chen WD, Yu D, Forman BM, Huang W. The G-protein-coupled bile acid receptor, Gpbarl (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor K light-chain enhancer of activated B cells (NF-KB) in mice. Hepatology 2011; 54:1421-1432 [PMID: 21735468 DOI: 10.1002/hep.24525]
92. Keitel V, Donner M, Winandy S, Kubitz R, Häussinger D. Expression and function of the bile acid receptor TGR5 in Kupffer cells. Biochem Biophys Res Commun 2008; 372: 78-84 [PMID: 18468513 DOI: 10.1016/j.bbrc.2008.04.171]
93. Péan N, Doignon I, Garcin I, Besnard A, Julien B, Liu B, Branchereau S, Spraul A, Guettier C, Humbert L, Schoonjans K, Rainteau D, Tordjmann T. The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice. Hepatology 2013; 58: 1451-1460 [PMID: 23686672 DOI: 10.1002/hep.26463]