• 1
    Martinez-Chantar ML, Vazquez-Chantada M, Ariz U, Martinez N, Varela M, Luka Z, et al. Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. HEPATOLOGY 2008; 47: 1191-1199.
  • 2
    Mudd SH, Cerone R, Schiaffino MC, Fantasia AR, Minniti G, Caruso U, et al. Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia. J Inherit Metab Dis 2001; 24: 448-464.
  • 3
    Augoustides-Savvopoulou P, Luka Z, Karyda S, Stabler SP, Allen RH, Patsiaoura K, et al. Glycine N-methyltransferase deficiency: a new patient with a novel mutation. J Inherit Metab Dis 2003; 26: 745-759.
  • 4
    Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A 1997; 94: 2557-2562.
  • 5
    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.
  • 6
    Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, et al. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci U S A 2006; 103: 12511-12516.
  • 7
    Li Z, Soloski MJ, Diehl AM. Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease. HEPATOLOGY 2005; 42: 880-885.
  • 8
    Guebre-Xabier M, Yang S, Lin HZ, Schwenk R, Krzych U, Diehl AM. Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: potential mechanism for sensitization to liver damage. HEPATOLOGY 2000; 31: 633-640.
  • 9
    Beraza N, Malato Y, Sander LE, Al-Masaoudi M, Freimuth J, Riethmacher D, et al. Hepatocyte-specific NEMO deletion promotes NK/NKT cell- and TRAIL-dependent liver damage. J Exp Med 2009; 206: 1727-1737.
  • 10
    Luka Z, Capdevila A, Mato JM, Wagner C. A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme. Transgenic Res 2006; 15: 393-397.
  • 11
    Avila MA, Berasain C, Torres L, Martin-Duce A, Corrales FJ, Yang H, et al. Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J Hepatol 2000; 33: 907-914.
  • 12
    Barr J, Vazquez-Chantada M, Alonso C, Perez-Cormenzana M, Mayo R, Galan A, et al. Liquid chromatography-mass spectrometry-based parallel metabolic profiling of human and mouse model serum reveals putative biomarkers associated with the progression of nonalcoholic fatty liver disease. J Proteome Res 2010; 9: 4501-4512.
  • 13
    Malhi H, Barreyro FJ, Isomoto H, Bronk SF, Gores GJ. Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity. Gut 2007; 56: 1124-1131.
  • 14
    Higuchi H, Bronk SF, Takikawa Y, Werneburg N, Takimoto R, El-Deiry W, et al. The bile acid glycochenodeoxycholate induces trail- receptor 2/DR5 expression and apoptosis. J Biol Chem 2001; 276: 38610-38618.
  • 15
    Nice TJ, Coscoy L, Raulet DH. Posttranslational regulation of the NKG2D ligand Mult1 in response to cell stress. J Exp Med 2009; 206: 287-298.
  • 16
    Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 2001; 413: 165-171.
  • 17
    Gao B. Natural killer group 2 member D, its ligands, and liver disease: good or bad? HEPATOLOGY 2010; 51: 8-11.
  • 18
    Takeda K, Hayakawa Y, Van Kaer L, Matsuda H, Yagita H, Okumura K. Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc Natl Acad Sci U S A 2000; 97: 5498-5503.
  • 19
    Toyabe S, Seki S, Iiai T, Takeda K, Shirai K, Watanabe H, et al. Requirement of IL-4 and liver NK1+ T cells for concanavalin A-induced hepatic injury in mice. J Immunol 1997; 159: 1537-1542.
  • 20
    Smyth MJ, Cretney E, Takeda K, Wiltrout RH, Sedger LM, Kayagaki N, et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. J Exp Med 2001; 193: 661-670.
  • 21
    Takeda K, Hayakawa Y, Smyth MJ, Kayagaki N, Yamaguchi N, Kakuta S, et al. Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med 2001; 7: 94-100.
  • 22
    Hasselblatt P, Rath M, Komnenovic V, Zatloukal K, Wagner EF. Hepatocyte survival in acute hepatitis is due to c-Jun/AP-1-dependent expression of inducible nitric oxide synthase. Proc Natl Acad Sci U S A 2007; 104: 17105-17110.
  • 23
    Matsui K, Yoshimoto T, Tsutsui H, Hyodo Y, Hayashi N, Hiroishi K, et al. Propionibacterium acnes treatment diminishes CD4+ NK1.1+ T cells but induces type I T cells in the liver by induction of IL-12 and IL-18 production from Kupffer cells. J Immunol 1997; 159: 97-106.
  • 24
    Varela-Rey M, Martinez-Lopez N, Fernandez-Ramos D, Embade N, Calvisi DF, Woodhoo A, et al. Fatty liver and fibrosis in glycine N-methyltransferase knockout mice is prevented by nicotinamide. HEPATOLOGY 2010; 52: 105-114.
  • 25
    Matsumoto A, Kinoshita M, Ono S, Tsujimoto H, Majima T, Habu Y, et al. Cooperative IFN-gamma production of mouse liver B cells and natural killer cells stimulated with lipopolysaccharide. J Hepatol 2006; 45: 290-298.
  • 26
    Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palu G, et al. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. American journal of physiology. Gastrointest Liver Physiol 2007; 292: G518-525.
  • 27
    Herr I, Wilhelm D, Meyer E, Jeremias I, Angel P, Debatin KM. JNK/SAPK activity contributes to TRAIL-induced apoptosis. Cell Death Differ 1999; 6: 130-135.
  • 28
    Muhlenbeck F, Haas E, Schwenzer R, Schubert G, Grell M, Smith C, et al. TRAIL/Apo2L activates c-Jun NH2-terminal kinase (JNK) via caspase-dependent and caspase-independent pathways. J Biol Chem 1998; 273: 33091-33098.
  • 29
    Lu SC, Alvarez L, Huang ZZ, Chen L, An W, Corrales FJ, et al. Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc Natl Acad Sci U S A 2001; 98: 5560-5565.