PMID- 15466479
OWN - NLM
STAT- MEDLINE
DCOM- 20050204
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 51
DP  - 2004 Dec 17
TI  - Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an 
      animal model for hyperhomocysteinemia.
PG  - 52961-9
AB  - Hyperhomocysteinemia (HHCY) is a consequence of impaired methionine/cysteine 
      metabolism and is caused by deficiency of vitamins and/or enzymes such as 
      cystathionine beta-synthase (CBS). Although HHCY is an important and independent 
      risk factor for cardiovascular diseases that are commonly associated with hepatic 
      steatosis, the mechanism by which homocysteine promotes the development of fatty 
      liver is poorly understood. CBS-deficient (CBS(-/-)) mice were previously 
      generated by targeted deletion of the Cbs gene and exhibit pathological features 
      similar to HHCY patients, including endothelial dysfunction and hepatic 
      steatosis. Here we show abnormal lipid metabolism in CBS(-/-) mice. Triglyceride 
      and nonesterified fatty acid levels were markedly elevated in CBS(-/-) mouse 
      liver and serum. The activity of thiolase, a key enzyme in beta-oxidation of 
      fatty acids, was significantly impaired in CBS(-/-) mouse liver. Hepatic 
      apolipoprotein B100 levels were decreased, whereas serum apolipoprotein B100 and 
      very low density lipoprotein levels were elevated in CBS(-/-) mice. Serum levels 
      of cholesterol/phospholipid in high density lipoprotein fractions but not of 
      total cholesterol/phospholipid were decreased, and the activity of 
      lecithin-cholesterol acyltransferase was severely impaired in CBS(-/-) mice. 
      Abnormal high density lipoprotein particles with higher mobility in 
      polyacrylamide gel electrophoresis were observed in serum obtained from CBS(-/-) 
      mice. Moreover, serum cholesterol/triglyceride distribution in lipoprotein 
      fractions was altered in CBS(-/-) mice. These results suggest that hepatic 
      steatosis in CBS(-/-) mice is caused by or associated with abnormal lipid 
      metabolism.
FAU - Namekata, Kazuhiko
AU  - Namekata K
AD  - National Institute of Neuroscience, National Center of Neurology and Psychiatry, 
      Ogawahigashi 4-1-1, Kodaira, Tokyo 187-8551, Japan.
FAU - Enokido, Yasushi
AU  - Enokido Y
FAU - Ishii, Isao
AU  - Ishii I
FAU - Nagai, Yasuo
AU  - Nagai Y
FAU - Harada, Takayuki
AU  - Harada T
FAU - Kimura, Hideo
AU  - Kimura H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041004
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Apolipoprotein B-100)
RN  - 0 (Apolipoproteins B)
RN  - 0 (Lipoproteins)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (Triglycerides)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.3.1.43 (Phosphatidylcholine-Sterol O-Acyltransferase)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apolipoprotein B-100
MH  - Apolipoproteins B/blood
MH  - Blotting, Northern
MH  - Cholesterol/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Cystathionine beta-Synthase/*genetics
MH  - Disease Models, Animal
MH  - Electrophoresis, Agar Gel
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Endothelium, Vascular/metabolism
MH  - Gene Expression Regulation
MH  - Genotype
MH  - Heterozygote
MH  - Homocysteine/genetics
MH  - Homozygote
MH  - Hyperhomocysteinemia/*genetics/metabolism
MH  - *Lipid Metabolism
MH  - Lipoproteins/metabolism
MH  - Lipoproteins, HDL/metabolism
MH  - Lipoproteins, LDL/metabolism
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Oxygen/metabolism
MH  - Phosphatidylcholine-Sterol O-Acyltransferase/metabolism
MH  - RNA, Messenger/metabolism
MH  - Risk Factors
MH  - Sulfhydryl Compounds/metabolism
MH  - Time Factors
MH  - Tissue Distribution
MH  - Triglycerides/metabolism
EDAT- 2004/10/07 09:00
MHDA- 2005/02/05 09:00
CRDT- 2004/10/07 09:00
PHST- 2004/10/07 09:00 [pubmed]
PHST- 2005/02/05 09:00 [medline]
PHST- 2004/10/07 09:00 [entrez]
AID - S0021-9258(18)81928-7 [pii]
AID - 10.1074/jbc.M406820200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Dec 17;279(51):52961-9. doi: 10.1074/jbc.M406820200. Epub 2004 
      Oct 4.