Methionine deficiency and hepatic injury in a dietary steatohepatitis model.
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).
Oz
Helieh S
HS
Center for the Oral Health Research, Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA. Helieh.oz@uky.edu
Chen
Theresa S
TS
Neuman
Manuela
M
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
D008715:Methionine
Hepatology. 2000 Mar;31(3):674-83
10706558
Transl Res. 2007 Aug;150(2):122-9
17656332
Hepatology. 2000 Jul;32(1):3-10
10869282
Mayo Clin Proc. 2000 Jul;75(7):733-9
10907390
Mech Ageing Dev. 2000 Dec 1;120(1-3):127-39
11087910
J Hepatol. 2000 Nov;33(5):716-24
11097478
Arch Biochem Biophys. 2002 Jan 15;397(2):172-8
11795868
N Engl J Med. 2002 Apr 18;346(16):1221-31
11961152
J Hepatol. 2002 Jul;37(1):56-62
12076862
Biochem J. 2003 Mar 15;370(Pt 3):987-93
12466019
Hepatology. 2003 May;37(5):1202-19
12717402
Hepatology. 2003 Aug;38(2):428-35
12883487
Gastroenterology. 2003 Aug;125(2):437-43
12891546
J Hepatol. 2003 Nov;39(5):756-64
14568258
Am J Med. 2003 Nov;115(7):554-9
14599635
J Int Med Res. 2003 Nov-Dec;31(6):537-51
14708419
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1159-64
14745014
Biochem Biophys Res Commun. 2004 Mar 12;315(3):699-703
14975757
Am J Clin Nutr. 2004 Mar;79(3):502-9
14985228
J Hepatol. 2004 Jun;40(6):917-25
15158331
J Clin Invest. 2004 Jul;114(2):147-52
15254578
Clin Liver Dis. 2004 Aug;8(3):595-617, x
15331066
Prog Food Nutr Sci. 1986;10(1-2):133-78
3538184
Hepatology. 1990 Jan;11(1):74-80
2295475
Mol Pharmacol. 1991 Mar;39(3):275-80
2005876
Eur J Pharmacol. 1995 Dec 7;293(4):385-93
8748692
Gastroenterology. 1996 Dec;111(6):1645-53
8942745
Hepatology. 1998 Jan;27(1):128-33
9425928
Am J Physiol. 1998 Jul;275(1 Pt 1):G125-9
9655692
Biochem Biophys Res Commun. 1999 Feb 16;255(2):300-6
10049703
Hepatology. 1999 Apr;29(4):1131-8
10094957
Gastroenterology. 1999 Jun;116(6):1413-9
10348825
Alcohol. 2004 Aug;34(1):67-79
15670668
J Biochem Mol Toxicol. 2004;18(6):361-8
15674847
J Nutr Biochem. 2005 May;16(5):297-304
15866230
J Hepatol. 2005 Jun;42(6):928-40
15885365
Eur Rev Med Pharmacol Sci. 2005 Sep-Oct;9(5):273-7
16231589
Hepatology. 2006 Feb;43(2 Suppl 1):S99-S112
16447287
Mitochondrion. 2006 Feb;6(1):1-28
16406828
J Biochem Mol Toxicol. 2006;20(1):39-47
16498637
Am J Gastroenterol. 2006 Mar;101(3):664-8
16464222
Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G852-8
16603729
Diabetologia. 2006 Aug;49(8):1732-41
16718463
Hepatology. 2007 Feb;45(2):391-403
17256749
Int J Biochem Cell Biol. 2000 Apr;32(4):391-5
10762064