Liver fibrogenesis and metabolic factors

Clinics and Research in Hepatology and Gastroenterology

Volumn 35, Issue , 2011, Pages S10-S20

  Anty, Rodolphe ^a,b,c   Lemoine, Maud ^d,e  

^a INSERM   (France)

^b UNIVERSITY HOSPITAL OF NICE   (France)

^c UNIVERSITÉ CÔTE D'AZUR   (France)

^d HÔPITAL SAINT ANTOINE   (France)

^e SORBONNE UNIVERSITÉ   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; BIOLOGICAL MARKER; ENDOCANNABINOID; INTERLEUKIN 6; LEPTIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA;

ARTICLE; BODY MASS; FATTY LIVER; HUMAN; KUPFFER CELL; LIVER CIRRHOSIS; METABOLIC SYNDROME X; METABOLISM; RISK FACTOR; STELLATE CELL;

ADIPOKINES; ADIPONECTIN; BIOLOGICAL MARKERS; BODY MASS INDEX; ENDOCANNABINOIDS; FATTY LIVER; HEPATIC STELLATE CELLS; HUMANS; INTERLEUKIN-6; KUPFFER CELLS; LEPTIN; LIVER CIRRHOSIS; METABOLIC SYNDROME X; PPAR GAMMA; RISK FACTORS;

MLCS; MLOWN;

EID: 80655137355     PISSN: 22107401     EISSN: 2210741X     Source Type: Journal    
DOI: 10.1016/S2210-7401(11)70003-1     Document Type: Article

References (134)

1. Rombouts, K., Marra, F., Molecular mechanisms of hepatic fibrosis in non-alcoholic steatohepatitis. Dig Dis 28 (2010), 229–235.
2. Lanthier, N., Horsmans, Y., Leclercq, I.A., The metabolic syndrome: how it may influence hepatic stellate cell activation and hepatic fibrosis. Curr Opin Clin Nutr Metab Care 12 (2009), 404–411.
3. Leclercq, I.A., Da Silva Morais, A., Schroyen, B., Van Hul, N., Geerts, A., Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. J Hepatol 47 (2007), 142–156.
4. van der Poorten, D., Milner, K.L., Hui, J., Hodge, A., Trenell, M.I., Kench, J.G., et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 48 (2008), 449–457.
5. Williams, C.D., Stengel, J., Asike, M.I., Torres, D.M., Shaw, J., Contreras, M., et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 140 (2011), 124–131.
6. Day, C., James, O., Steatohepatitis: a tale of two «hits» ?. Gastroenterology 114 (1998), 842–845.
7. Friedman, S.L., Mechanisms of hepatic fibrogenesis. Gastroenterology 134 (2008), 1655–1669.
8. Friedman, S.L., Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 88 (2008), 125–172.
9. Alberti, K.G., Eckel, R.H., Grundy, S.M., Zimmet, P.Z., Cleeman, J.I., Donato, K.A., et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120 (2009), 1640–1645.
10. Wallace, T.M., Matthews, D.R., The assessment of insulin resistance in man. Diabet Med 19 (2002), 527–534.
11. Papatheodoridis, G.V., Hadziyannis, E., Tsochatzis, E., Georgiou, A., Kafiri, G., Tiniakos, D.G., et al. Serum apoptotic caspase activity in chronic hepatitis C and nonalcoholic Fatty liver disease. J Clin Gastroenterol 44 (2010), e87–e95.
12. Porepa, L., Ray, J.G., Sanchez-Romeu, P., Booth, G.L., Newly diagnosed diabetes mellitus as a risk factor for serious liver disease. Cmaj 182 (2010), E526–E531.
13. Garcia-Compean, D., Jaquez-Quintana, J.O., Maldonado-Garza, H., Hepatogenous diabetes. Current views of an ancient problem. Ann Hepatol 8 (2009), 13–20.
14. Calle, E.E., Rodriguez, C., Walker-Thurmond, K., Thun, M.J., Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348 (2003), 1625–1638.
15. Hassan, M.M., Curley, S.A., Li, D., Kaseb, A., Davila, M., Abdalla, E.K., et al. Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer 116 (2010), 1938–1946.
16. Donadon, V., Balbi, M., Casarin, P., Vario, A., Alberti, A., Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy: potential role of insulin. World J Gastroenterol 14 (2008), 5695–5700.
17. Sorrentino, P., Terracciano, L., D'Angelo, S., Ferbo, U., Bracigliano, A., Vecchione, R., Predicting fibrosis worsening in obese patients with NASH through parenchymal fibronectin, HOMA-IR, and hypertension. Am J Gastroenterol 105 (2010), 336–344.
18. Ban, C.R., Twigg, S.M., Fibrosis in diabetes complications: pathogenic mechanisms and circulating and urinary markers. Vasc Health Risk Manag 4 (2008), 575–596.
19. Svegliati-Baroni, G., Ridolfif, F., Di Sario, A., Casini, A., Marucci, L., Gaggiotti, G., et al. Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. Hepatology 29 (1999), 1743–1751.
20. Paradis, V., Perlemuter, G., Bonvoust, F., Dargere, D., Parfait, B., Vidaud, M., et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology 34 (2001), 738–744.
21. Castilla-Cortazar, I., Garcia, M., Muguerza, B., Quiroga, J., Perez, R., Santidrian, S., et al. Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis. Gastroenterology 113 (1997), 1682–1691.
22. Svegliati-Baroni, G., Faraci, G., Fabris, L., Saccomanno, S., Cadamuro, M., Pierantonelli, I., et al. Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C. Gut 60 (2011), 108–115.
23. Fehrenbach, H., Weiskirchen, R., Kasper, M., Gressner, A.M., Up-regulated expression of the receptor for advanced glycation end products in cultured rat hepatic stellate cells during transdifferentiation to myofibroblasts. Hepatology 34 (2001), 943–952.
24. Syn, W.K., Choi, S.S., Liaskou, E., Karaca, G.F., Agboola, K.M., Oo, Y.H., et al. Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis. Hepatology, 20, 2010, 20.
25. Bertola, A., Deveaux, V., Bonnafous, S., Rousseau, D., Anty, R., Wakkach, A., et al. Elevated expression of osteopontin may be related to adipose tissue macrophage accumulation and liver steatosis in morbid obesity. Diabetes 58 (2009), 125–133.
26. Bertola, A., Bonnafous, S., Anty, R., Patouraux, S., Saint-Paul, M.C., Iannelli, A., et al. Hepatic expression patterns of inflammatory and immune response genes associated with obesity and NASH in morbidly obese patients. PLoS One, 5, 2010, e13577.
27. Syn, W.K., Choi, S.S., Diehl, A.M., Apoptosis and cytokines in nonalcoholic steatohepatitis. Clin Liver Dis 13 (2009), 565–580.
28. Wieckowska, A., Zein, N.N., Yerian, L.M., Lopez, A.R., McCullough, A.J., Feldstein, A.E., In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 44 (2006), 27–33.
29. Anty, R., Iannelli, A., Patouraux, S., Bonnafous, S., Lavallard, V.J., Senni-Buratti, M., et al. A new composite model including metabolic syndrome, alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients. Aliment Pharmacol Ther 32 (2010), 1315–1322 doi: 10.1111/j.1365-2036.2010.04480.x.
30. Fitzpatrick, E., Mitry, R.R., Quaglia, A., Hussain, M.J., DeBruyne, R., Dhawan, A., Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and fibrosis in paediatric NAFLD. J Pediatr Gastroenterol Nutr 51 (2010), 500–506.
31. Lavallard, V.J., Bonnafous, S., Patouraux, S., Saint-Paul, M.C., Rousseau, D., Anty, R., et al. Serum markers of hepatocyte death and apoptosis are non invasive biomarkers of severe fibrosis patients with alcoholic liver disease. PLoS One, 2011, 18 doi:10.1371/journal.pone.0017599.
32. Krizhanovsky, V., Yon, M., Dickins, R.A., Hearn, S., Simon, J., Miething, C., et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134 (2008), 657–667.
33. Cao, J., Kozarekar, P., Pavlaki, M., Chiarelli, C., Bahou, W.F., Zucker, S., Distinct roles for the catalytic and hemopexin domains of membrane type 1-matrix metalloproteinase in substrate degradation and cell migration. J Biol Chem 279 (2004), 14129–14139.
34. Muhanna, N., Abu Tair, L., Doron, S., Amer, J., Azzeh, M., Mahamid, M., et al. Amelioration of hepatic fibrosis by NK cell activation. Gut 60 (2011), 90–98.
35. Syn, W.K., Oo, Y.H., Pereira, T.A., Karaca, G.F., Jung, Y., Omenetti, A., et al. Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 51 (2010), 1998–2007.
36. Donnelly, K.L., Smith, C.I., Schwarzenberg, S.J., Jessurun, J., Boldt, M.D., Parks, E.J., Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115 (2005), 1343–1351.
37. Fabbrini, E., Mohammed, B.S., Magkos, F., Korenblat, K.M., Patterson, B.W., Klein, S., Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology 134 (2008), 424–431.
38. Bugianesi, E., Gastaldelli, A., Vanni, E., Gambino, R., Cassader, M., Baldi, S., et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia 48 (2005), 634–642.
39. Sanyal, A.J., Campbell-sargent, C., Mirshahi, F., Rizzo, W.B., Contos, M.J., Sterling, R.K., et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120 (2001), 1183–1192.
40. Chalasani, N., Gorski, J.C., Asghar, M.S., Asghar, A., Foresman, B., Hall, S.D., et al. Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis. Hepatology 37 (2003), 544–550.
41. Kotronen, A., Seppala-Lindroos, A., Vehkavaara, S., Bergholm, R., Frayn, K.N., Fielding, B.A., et al. Liver fat and lipid oxidation in humans. Liver Int 29 (2009), 1439–1446.
42. Korenblat, K.M., Fabbrini, E., Mohammed, B.S., Klein, S., Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects. Gastroenterology 134 (2008), 1369–1375.
43. Fabbrini, E., Magkos, F., Mohammed, B.S., Pietka, T., Abumrad, N.A., Patterson, B.W., et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci U S A 106 (2009), 15430–15435.
44. Vega, G.L., Chandalia, M., Szczepaniak, L.S., Grundy, S.M., Metabolic correlates of nonalcoholic fatty liver in women and men. Hepatology 46 (2007), 716–722.
45. Adams, L.A., Lymp, J.F., St Sauver, J., Sanderson, S.O., Lindor, K.D., Feldstein, A., et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129 (2005), 113–121.
46. Ekstedt, M., Franzen, L.E., Mathiesen, U.L., Thorelius, L., Holmqvist, M., Bodemar, G., et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44 (2006), 865–873.
47. Wong, V.W., Wong, G.L., Choi, P.C., Chan, A.W., Li, M.K., Chan, H.Y., et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 59 (2010), 969–974.
48. Amaro, A., Fabbrini, E., Kars, M., Yue, P., Schechtman, K., Schonfeld, G., et al. Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia. Gastroenterology 139 (2010), 149–153.
49. Yamaguchi, K., Yang, L., McCall, S., Huang, J., Yu, X.X., Pandey, S.K., et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45 (2007), 1366–1374.
50. Monetti, M., Levin, M.C., Watt, M.J., Sajan, M.P., Marmor, S., Hubbard, B.K., et al. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab 6 (2007), 69–78.
51. Kantartzis, K., Machicao, F., Machann, J., Schick, F., Fritsche, A., Haring, H.U., et al. The DGAT2 gene is a candidate for the dissociation between fatty liver and insulin resistance in humans. Clin Sci (Lond) 116 (2009), 531–537.
52. Kantartzis, K., Peter, A., Machicao, F., Machann, J., Wagner, S., Konigsrainer, I., et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 58 (2009), 2616–2623.
53. Garcia-Monzon, C., Martin-Perez, E., Iacono, O.L., Fernandez-Bermejo, M., Majano, P.L., Apolinario, A., et al. Characterization of pathogenic and prognostic factors of nonalcoholic steatohepatitis associated with obesity. J Hepatol 33 (2000), 716–724.
54. Hazra, S., Xiong, S., Wang, J., Rippe, R.A., Krishna, V., Chatterjee, K., et al. Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from activated to quiescent hepatic stellate cells. J Biol Chem 279 (2004), 11392–11401.
55. Galli, A., Crabb, D.W., Ceni, E., Salzano, R., Mello, T., Svegliati-Baroni, G., et al. Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. Gastroenterology 122 (2002), 1924–1940.
56. Gupte, A.A., Liu, J.Z., Ren, Y., Minze, L.J., Wiles, J.R., Collins, A.R., et al. Rosiglitazone attenuates age- and diet-associated nonalcoholic steatohepatitis in male low-density lipoprotein receptor knockout mice. Hepatology 52 (2010), 2001–2011 doi: 10.1002/hep.23941.
57. Sanyal, A.J., Chalasani, N., Kowdley, K.V., McCullough, A., Diehl, A.M., Bass, N.M., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362 (2010), 1675–1685.
58. Ratziu, V., Giral, P., Jacqueminet, S., Charlotte, F., Hartemann-Heurtier, A., Serfaty, L., et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 135 (2008), 100–110.
59. Lemoine, M., Barbu, V., Girard, P.M., Kim, M., Bastard, J.P., Wendum, D., et al. Altered hepatic expression of SREBP-1 and PPARgamma is associated with liver injury in insulin-resistant lipodystrophic HIV-infected patients. Aids 20 (2006), 387–395.
60. Mallat, A., Lotersztajn, S., Endocannabinoids as novel mediators of liver diseases. J Endocrinol Invest 29 (2006), 58–65.
61. Mallat, A., Teixeira-Clerc, F., Deveaux, V., Lotersztajn, S., Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases. Expert Opin Ther Targets 11 (2007), 403–409.
62. Cota, D., Marsicano, G., Tschop, M., Grubler, Y., Flachskamm, C., Schubert, M., et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 112 (2003), 423–431.
63. Osei-Hyiaman, D., DePetrillo, M., Pacher, P., Liu, J., Radaeva, S., Batkai, S., et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 115 (2005), 1298–1305.
64. Teixeira-Clerc, F., Julien, B., Grenard, P., Tran Van Nhieu, J., Deveaux, V., Li, L., et al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med 12 (2006), 671–676.
65. Batkai, S., Jarai, Z., Wagner, J.A., Goparaju, S.K., Varga, K., Liu, J., et al. Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med 7 (2001), 827–832.
66. Ros, J., Claria, J., To-Figueras, J., Planaguma, A., Cejudo-Martin, P., Fernandez-Varo, G., et al. Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology 122 (2002), 85–93.
67. Julien, B., Grenard, P., Teixeira-Clerc, F., Van Nhieu, J.T., Li, L., Karsak, M., et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 128 (2005), 742–755.
68. Hezode, C., Roudot-Thoraval, F., Nguyen, S., Grenard, P., Julien, B., Zafrani, E.S., et al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 42 (2005), 63–71.
69. Pacher, P., Batkai, S., Kunos, G., The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58 (2006), 389–462.
70. Chuang, J.H., Wang, P.W., Tai, M.H., An adipocentric view of liver fibrosis and cirrhosis. Chang Gung Med J 27 (2004), 855–868.
71. Friedman, J., Halaas, J., Leptin and the regulation of body weight in mammals. Nature 395 (1998), 763–770.
72. Honda, H., Ikejima, K., Hirose, M., Yoshikawa, M., Lang, T., Enomoto, N., et al. Leptin is required for fibrogenic responses induced by thioacetamide in the murine liver. Hepatology 36 (2002), 12–21.
73. Leclercq, I.A., Field, J., Farrell, G.C., Leptin-specific mechanisms for impaired liver regeneration in ob/ob mice after toxic injury. Gastroenterology 124 (2003), 1451–1464.
74. Ikejima, K., Takei, Y., Honda, H., Hirose, M., Yoshikawa, M., Zhang, Y., et al. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 122 (2002), 1399–1410.
75. Ikejima, K., Honda, H., Yoshikawa, M., Hirose, M., Kitamura, T., Takei, Y., et al. Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals. Hepatology 34 (2001), 288–297.
76. Rieder, H., Armbrust, T., Meyer zum Buschenfelde, K.H., Ramadori, G., Contribution of sinusoidal endothelial liver cells to liver fibrosis: expression of transforming growth factor-beta 1 receptors and modulation of plasmin-generating enzymes by transforming growth factor-beta 1. Hepatology 18 (1993), 937–944.
77. Lemoine, M., Ratziu, V., Kim, M., Maachi, M., Wendum, D., Paye, F., et al. Serum adipokine levels predictive of liver injury in non-alcoholic fatty liver disease. Liver Int 29 (2009), 1431–1438.
78. Potter, J., Womack, L., Mezey, E., Anania, F., Transdifferentiation of rat hepatic stellate cell results in leptin expression. Biochem Biophys Res Commun 244 (1998), 178–182.
79. Mantzoros, C.S., Moschos, S., Avramopoulos, I., Kaklamani, V., Liolios, A., Doulgerakis, D.E., et al. Leptin concentrations in relation to body mass index and the tumor necrosis factor-alpha system in humans. J Clin Endocrinol Metab 82 (1997), 3408–3413.
80. Uygun, A., Kadayifci, A., Yesilova, Z., Erdil, A., Yaman, H., Saka, M., et al. Serum leptin levels in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 95 (2000), 3584–3589.
81. Chalasani, N., Crabb, D.W., Cummings, O.W., Kwo, P.Y., Asghar, A., Pandya, P.K., et al. Does leptin play a role in the pathogenesis of human nonalcoholic steatohepatitis?. Am J Gastroenterol 98 (2003), 2771–2776.
82. Angulo, P., Alba, L.M., Petrovic, L.M., Adams, L.A., Lindor, K.D., Jensen, M.D., Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease. J Hepatol 41 (2004), 943–949.
83. Henriksen, J.H., Holst, J.J., Moller, S., Brinch, K., Bendtsen, F., Increased circulating leptin in alcoholic cirrhosis: relation to release and disposal. Hepatology 29 (1999), 1818–1824.
84. McCullough, A.J., Bugianesi, E., Marchesini, G., Kalhan, S.C., Genderdependent alterations in serum leptin in alcoholic cirrhosis. Gastroenterology 115 (1998), 947–953.
85. Comlekci, A., Akpinar, H., Yesil, S., Okan, I., Ellidokuz, E., Okan, A., et al. Serum leptin levels in patients with liver cirrhosis and chronic viral hepatitis. Scand J Gastroenterol 38 (2003), 779–786.
86. Lin, H.Z., Yang, S.Q., Zeldin, G., Diehl, A.M., Chronic ethanol consumption induces the production of tumor necrosis factor-alpha and related cytokines in liver and adipose tissue. Alcohol Clin Exp Res 22 (1998), 231S–237S.
87. Piche, T., Vandenbos, T., Abakar-Mahamat, A., Vanbiervliet, G., Mariné-Barjoan, E., Calle, G., et al. The severity of liver fibrosis is associated with high leptin levels in chronic hepatitis C. J Viral Hepatitis 11 (2004), 91–96.
88. Crespo, J., Rivero, M., Fabrega, E., Cayon, A., Amado, J.A., Garcia-Unzeta, M.T., et al. Plasma leptin and TNF-alpha levels in chronic hepatitis C patients and their relationship to hepatic fibrosis. Dig Dis Sci 47 (2002), 1604–1610.
89. Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J., et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 257 (1999), 79–83.
90. Kadowaki, T., Yamauchi, T., Kubota, N., Hara, K., Ueki, K., Tobe, K., Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116 (2006), 1784–1792.
91. Diez, J.J., Iglesias, P., The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 148 (2003), 293–300.
92. Berg, A.H., Combs, T.P., Du, X., Brownlee, M., Scherer, P.E., The adipocyte-secreted protein acrp30 enhances hepatic insulin action. Nat Med 7 (2001), 947–953.
93. Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423 (2003), 762–769.
94. Buechler, C., Wanninger, J., Neumeier, M., Adiponectin receptor binding proteins–recent advances in elucidating adiponectin signalling pathways. FEBS Lett 584 (2010), 4280–4286.
95. Fasshauer, M., Klein, J., Neumann, S., Eszlinger, M., Paschke, R., Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 290 (2002), 1084–1089.
96. Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8 (2002), 731–737.
97. Xu, A., Wang, Y., Keshaw, H., Xu, L.Y., Lam, K.S., Cooper, G.J., The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J clin Invest 112 (2003), 91–100.
98. Masaki, T., Chiba, S., Tatsukawa, H., Yasuda, T., Noguchi, H., Seike, M., et al. Adiponectin protects LPS-induced liver injury through modulation of TNF-a in KK-Ay obese mice. Hepatology 40 (2004), 177–184.
99. Yoda-Murakami, M., Taniguchi, M., Takahashi, K., Kawamata, S., Saito, K., Choi-Miura, N.H., et al. Change in expression of GBP28/adiponectin in carbon tetrachloride-administered mouse liver. Biochem Biophys Res Commun 285 (2001), 372–377.
100. Tomita, K., Oike, Y., Teratani, T., Taguchi, T., Noguchi, M., Suzuki, T., et al. Hepatic AdipoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis in mice. Hepatology 48 (2008), 458–473.
101. Hui, J.M., Hodge, A., Farrell, G.C., Kench, J.G., Kriketos, A., George, J., Beyond insulin resistance in NASH: TNF-alpha or adiponectin?. Hepatology 40 (2004), 46–54.
102. Kaser, S., Moschen, A., Cayon, A., Kaser, A., Crespo, J., Pons-Romero, F., et al. Adiponectin and its receptors in non-alcoholic steatohepatitis. Gut 54 (2005), 117–121.
103. Vuppalanchi, R., Marri, S., Kolwankar, D., Considine, R.V., Chalasani, N., Is adiponectin involved in the pathogenesis of nonalcoholic steatohepatitis? A preliminary human study. J Clin Gastroenterol 39 (2005), 237–242.
104. Ma, H., Gomez, V., Lu, L., Yang, X., Wu, X., Xiao, S.Y., Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol 24 (2009), 233–237.
105. Bansal, M.B., Kovalovich, K., Gupta, R., Li, W., Agarwal, A., Radbill, B., et al. Interleukin-6 protects hepatocytes from CCl4-mediated necrosis and apoptosis in mice by reducing MMP-2 expression. J Hepatol 42 (2005), 548–556.
106. Hong, F., Radaeva, S., Pan, H.N., Tian, Z., Veech, R., Gao, B., Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease. Hepatology 40 (2004), 933–941.
107. Jin, X., Zimmers, T.A., Perez, E.A., Pierce, R.H., Zhang, Z., Koniaris, L.G., Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair. Hepatology 43 (2006), 474–484.
108. Yamaguchi, K., Itoh, Y., Yokomizo, C., Nishimura, T., Niimi, T., Fujii, H., et al. Blockade of interleukin-6 signaling enhances hepatic steatosis but improves liver injury in methionine cholinedeficient diet-fed mice. Lab Invest 90 (2010), 1169–1178.
109. Hill, D.B., Marsano, L., Cohen, D., Allen, J., Shedlofsky, S., McClain, C.J., Increased plasma interleukin-6 concentrations in alcoholic hepatitis. J Lab Clin Med 119 (1992), 547–552.
110. Kugelmas, M., Hill, D.B., Vivian, B., Marsano, L., McClain, C.J., Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 38 (2003), 413–419.
111. Marra, F., Bertolani, C., Adipokines in liver diseases. Hepatology 50 (2009), 957–969.
112. Bays, H., Blonde, L., Rosenson, R., Adiposopathy: how do diet, exercise and weight loss drug therapies improve metabolic disease in overweight patients?. Expert Rev Cardiovasc Ther 4 (2006), 871–895.
113. Sell, H., Eckel, J., Adipose tissue inflammation: novel insight into the role of macrophages and lymphocytes. Curr Opin Clin Nutr Metab Care 13 (2010), 366–370.
114. Neuschwander-Tetri, B.A., Caldwell, S.H., Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology 37 (2003), 1202–1219.
115. McCullough, A.J., Thiazolidinediones for nonalcoholic steatohepatitis-promising but not ready for prime time. N Engl J Med 355 (2006), 2361–2363.
116. Fracanzani, A.L., Valenti, L., Bugianesi, E., Vanni, E., Grieco, A., Miele, L., et al. Risk of non alcoholic steatohepatitis and fibrosis in patients with non alcoholic fatty liver disease and low visceral adiposity. J Hepatol, 11, 2010, 11.
117. Pataky, Z., Bobbioni-Harsch, E., Golay, A., Open questions about metabolically normal obesity. Int J Obes (Lond) 34 (2010), S18–S23.
118. Zimmermann, E., Anty, R., Tordjman, J., Verrijken, A., Gual, P., Tran, A., et al. C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients. J Hepatol, 13, 2011, 13.
119. Slawik, M., Vidal-Puig, A.J., Adipose tissue expandability and the metabolic syndrome. Genes Nutr 2 (2007), 41–45.
120. Lee, M.J., Wu, Y., Fried, S.K., Adipose tissue remodeling in pathophysiology of obesity. Curr Opin Clin Nutr Metab Care 13 (2010), 371–376.
121. Cheung, O., Kapoor, A., Puri, P., Sistrun, S., Luketic, V.A., Sargeant, C.C., et al. The impact of fat distribution on the severity of nonalcoholic fatty liver disease and metabolic syndrome. Hepatology 46 (2007), 1091–1100.
122. Nielsen, S., Guo, Z., Johnson, C.M., Hensrud, D.D., Jensen, M.D., Splanchnic lipolysis in human obesity. J Clin Invest 113 (2004), 1582–1588.
123. Fabbrini, E., Sullivan, S., Klein, S., Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 51 (2010), 679–689.
124. Petersen, K.F., Dufour, S., Befroy, D., Lehrke, M., Hendler, R.E., Shulman, G.I., Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 54 (2005), 603–608.
125. Alberti, K.G., Zimmet, P., Shaw, J., Metabolic syndrome–a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 23 (2006), 469–480.
126. Nolan, J.P., The role of intestinal endotoxin in liver injury: a long and evolving history. Hepatology 52 (2010), 1829–1835.
127. Marteau, P., The clinical importance of intestinal microbiota. Gastroenterol Clin Biol 34 (2010), S93–S97.
128. Backhed, F., Ding, H., Wang, T., Hooper, L.V., Koh, G.Y., Nagy, A., et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101 (2004), 15718–15723.
129. Turnbaugh, P.J., Ley, R.E., Mahowald, M.A., Magrini, V., Mardis, E.R., Gordon, J.I., An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444 (2006), 1027–1031.
130. Ley, R.E., Turnbaugh, P.J., Klein, S., Gordon, J.I., Microbial ecology: human gut microbes associated with obesity. Nature 444 (2006), 1022–1023.
131. Yan, A.W., Fouts, D.E., Brandl, J., Starkel, P., Torralba, M., Schott, E., et al. Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology, 30, 2010, 30.
132. Miele, L., Valenza, V., La Torre, G., Montalto, M., Cammarota, G., Ricci, R., et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 49 (2009), 1877–1887.
133. Vanni, E., Bugianesi, E., The gut-liver axis in nonalcoholic fatty liver disease: Another pathway to insulin resistance?. Hepatology 49 (2009), 1790–1792.
134. Spruss, A., Kanuri, G., Wagnerberger, S., Haub, S., Bischoff, S.C., Bergheim, I., Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology 50 (2009), 1094–1104.