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Changes in Liver Fads2 expression and Phospholipid Fatty Acids in Mice with Hyperhomocysteinemia
Author(s) -
Devlin Angela M.,
Innis Sheila M,
Wade Rachel E,
Boersma Heather M.,
Lentz Steven R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a859-b
Subject(s) - phosphatidylethanolamine , hyperhomocysteinemia , methionine , medicine , phospholipid , endocrinology , homocysteine , cystathionine beta synthase , phosphatidylcholine , methylation , transmethylation , fads2 , chemistry , metabolism , dna methylation , biochemistry , biology , gene expression , fatty acid , polyunsaturated fatty acid , gene , amino acid , docosahexaenoic acid , membrane
Homocysteine is metabolically linked to methylation reactions through the methionine cycle and we have previously shown that hyperhomocysteinemia (HHcy) is accompanied by reduced tissue methylation capacity and altered DNA methylation. Phospholipids are substrates for methylation reactions with phosphatidylcholine (PC) produced following methylation of phosphatidylethanolamine (PE). PC and PE are integral membrane lipids in the liver and we hypothesize that some of the pathological effects of HHcy may be related to changes in PC and PE metabolism. The goal of the present study was to determine the effect of HHcy on liver phospholipids, phospholipid fatty acids and transcripts for Fads2, which functions to desaturate 18:2n‐6 and 18:3n‐3 to 20:4n‐6 and 22:6n‐3, respectively. Mice heterozygous for disruption of the gene for cystathionine‐β‐synthase ( Cbs +/−) and C57BL/6 mice ( Cbs +/+) were fed a control diet or a high methionine/low folate diet to induce HHcy (HH diet) for 8–12 months. We found a higher percentage of PE (32.0±0.6 vs 26.4±0.5, p<0.001) and lower percentage of PC (41.0±1.1 vs 45.6±0.3, p<0.01) in liver phospholipids of Cbs +/−mice fed the HH diet with HHcy (95±12μmol/L) than Cbs +/+ mice fed the control diet. This was accompanied by lower (p<0.01) 20:4n‐6 in PC and PE, higher (p<0.01) 22:6n‐3 in PE, and lower (p<0.05) levels of Fads2 transcripts in liver from Cbs +/− fed the HH diet than Cbs +/+ mice fed the control diet. These findings are the first to show altered liver phospholipid fatty acids and Fads2 transcripts in a mouse model of HHcy and suggest a role for changes in phospholipid fatty acid metabolism in the pathology of HHcy.