title: Methionine deficiency and hepatic injury in a dietary steatohepatitis model.
abstract: Methionine (Meth) is an essential amino acid involved in DNA methylation and glutathione biosynthesis. We examined the effect of Meth on the development of steatohepatitis. Rats were fed (five weeks) amino acid-based Meth-choline-sufficient (A-MCS) or total deficient (MCD) diets and gavaged daily (two weeks) with vehicle (B-vehicle/MCD), or Meth replacement (C-Meth/MCD). To assess the effect of short-term deficiency, after three weeks one MCS group was fed a deficient diet (D-MCS/MCD). Animals fed the deficient diet for two weeks lost (29%) weight and after five weeks weighed one third as much as those on the sufficient diet, and also developed anemia (P < 0.01). Hepatic transaminases progressively increased from two to five weeks (P < 0.01), leading to severe hepatic pathology. Meth administration normalized hematocrit, improved weight (P < 0.05), and suppressed abnormal enzymes activities (P < 0.01). Meth administration improved blood and hepatic glutathione (GSH), S-adenosylmethionine (SAMe), and hepatic lesions (P < 0.01). The deficient diet significantly upregulated proinflammatory and fibrotic genes, which was ameliorated by Meth administration. These data support a pivotal role for methionine in the pathogenesis of the dietary model of Meth-choline-deficient (MCD) steatohepatitis (NASH).
authors: Center for the Oral Health Research, Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA. Helieh.oz@uky.edu
authors: Helieh S
authors: HS
authors: Oz
authors: Theresa S
authors: TS
authors: Chen
authors: Manuela
authors: M
authors: Neuman
mesh_terms: D000818:Animals; D002796:Choline Deficiency / Q000378:metabolism* / Q000473:pathology; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006520:Hepatitis, Animal / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008297:Male; D008715:Methionine / Q000172:deficiency*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008715:Methionine
references: Hepatology. 2000 Mar;31(3):674-83
references: 10706558
references: Transl Res. 2007 Aug;150(2):122-9
references: 17656332
references: Hepatology. 2000 Jul;32(1):3-10
references: 10869282
references: Mayo Clin Proc. 2000 Jul;75(7):733-9
references: 10907390
references: Mech Ageing Dev. 2000 Dec 1;120(1-3):127-39
references: 11087910
references: J Hepatol. 2000 Nov;33(5):716-24
references: 11097478
references: Arch Biochem Biophys. 2002 Jan 15;397(2):172-8
references: 11795868
references: N Engl J Med. 2002 Apr 18;346(16):1221-31
references: 11961152
references: J Hepatol. 2002 Jul;37(1):56-62
references: 12076862
references: Biochem J. 2003 Mar 15;370(Pt 3):987-93
references: 12466019
references: Hepatology. 2003 May;37(5):1202-19
references: 12717402
references: Hepatology. 2003 Aug;38(2):428-35
references: 12883487
references: Gastroenterology. 2003 Aug;125(2):437-43
references: 12891546
references: J Hepatol. 2003 Nov;39(5):756-64
references: 14568258
references: Am J Med. 2003 Nov;115(7):554-9
references: 14599635
references: J Int Med Res. 2003 Nov-Dec;31(6):537-51
references: 14708419
references: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1159-64
references: 14745014
references: Biochem Biophys Res Commun. 2004 Mar 12;315(3):699-703
references: 14975757
references: Am J Clin Nutr. 2004 Mar;79(3):502-9
references: 14985228
references: J Hepatol. 2004 Jun;40(6):917-25
references: 15158331
references: J Clin Invest. 2004 Jul;114(2):147-52
references: 15254578
references: Clin Liver Dis. 2004 Aug;8(3):595-617, x
references: 15331066
references: Prog Food Nutr Sci. 1986;10(1-2):133-78
references: 3538184
references: Hepatology. 1990 Jan;11(1):74-80
references: 2295475
references: Mol Pharmacol. 1991 Mar;39(3):275-80
references: 2005876
references: Eur J Pharmacol. 1995 Dec 7;293(4):385-93
references: 8748692
references: Gastroenterology. 1996 Dec;111(6):1645-53
references: 8942745
references: Hepatology. 1998 Jan;27(1):128-33
references: 9425928
references: Am J Physiol. 1998 Jul;275(1 Pt 1):G125-9
references: 9655692
references: Biochem Biophys Res Commun. 1999 Feb 16;255(2):300-6
references: 10049703
references: Hepatology. 1999 Apr;29(4):1131-8
references: 10094957
references: Gastroenterology. 1999 Jun;116(6):1413-9
references: 10348825
references: Alcohol. 2004 Aug;34(1):67-79
references: 15670668
references: J Biochem Mol Toxicol. 2004;18(6):361-8
references: 15674847
references: J Nutr Biochem. 2005 May;16(5):297-304
references: 15866230
references: J Hepatol. 2005 Jun;42(6):928-40
references: 15885365
references: Eur Rev Med Pharmacol Sci. 2005 Sep-Oct;9(5):273-7
references: 16231589
references: Hepatology. 2006 Feb;43(2 Suppl 1):S99-S112
references: 16447287
references: Mitochondrion. 2006 Feb;6(1):1-28
references: 16406828
references: J Biochem Mol Toxicol. 2006;20(1):39-47
references: 16498637
references: Am J Gastroenterol. 2006 Mar;101(3):664-8
references: 16464222
references: Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G852-8
references: 16603729
references: Diabetologia. 2006 Aug;49(8):1732-41
references: 16718463
references: Hepatology. 2007 Feb;45(2):391-403
references: 17256749
references: Int J Biochem Cell Biol. 2000 Apr;32(4):391-5
references: 10762064