PMID- 20018805 OWN - NLM STAT- MEDLINE DCOM- 20100204 LR - 20231213 IS - 1541-6100 (Electronic) IS - 0022-3166 (Linking) VI - 140 IP - 2 DP - 2010 Feb TI - Hepatic acyl-coenzyme a:cholesterol acyltransferase-2 expression is decreased in mice with hyperhomocysteinemia. PG - 231-7 LID - 10.3945/jn.109.112920 [doi] AB - Alterations in lipid metabolism may contribute to the pathology of hyperhomocysteinemia (HHcy). Our objective in this study was to test the hypothesis that HHcy is associated with changes in liver acyl CoA:cholesterol acyl transferase 2 (ACAT2) expression and cholesteryl esters (CE) in mice with HHcy. ACAT2 is encoded by Soat2 and functions to catalyze the esterification of cholesterol with acyl-CoA. Mice heterozygous for disruption of the cystathionine-beta-synthase gene (Cbs +/-) and C57BL/6 mice (Cbs +/+) were fed a control diet or a diet high in l-methionine (8.60 g/kg) and low in folic acid (0.20 mg/kg) to induce HHcy (HH diet). Lower Soat2 mRNA (P < 0.05) and ACAT protein (P < 0.001), higher total oleic acid [18:1(n-9)], and lower CE 18:1(n-9) was found in liver from Cbs +/- mice fed the HH diet, with higher plasma total homocysteine concentrations, than Cbs +/+ mice fed the control diet (35.01 +/- 5.6 vs. 2.21 +/- 0.6 mumol/L, respectively). In silico searches identified a CpG-rich region in the 5' portion of the Soat2 gene, which was differentially methylated (P < 0.05) in Cbs +/- mice fed the HH diet than in Cbs +/+ mice fed the control diet and was accompanied by higher (P < 0.05) B1 repeat element methylation, an indicator of global de novo methylation. These findings show altered methylation and expression of Soat2/ACAT2 in liver from mice with HHcy and suggest a role for changes in liver CE in the pathology of HHcy. FAU - Devlin, Angela M AU - Devlin AM AD - Department of Pathology and Laboratory Medicine, Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver V5Z 4H4, Canada. angela.devlin@ubc.ca FAU - Singh, Ranji AU - Singh R FAU - Bottiglieri, Teodoro AU - Bottiglieri T FAU - Innis, Sheila M AU - Innis SM FAU - Green, Tim J AU - Green TJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091216 PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (Acyl Coenzyme A) RN - 0 (Cholesterol Esters) RN - 0 (RNA, Messenger) RN - 0LVT1QZ0BA (Homocysteine) RN - 2UMI9U37CP (Oleic Acid) RN - AE28F7PNPL (Methionine) RN - EC 2.3.1.26 (Sterol O-Acyltransferase) RN - EC 4.2.1.22 (Cystathionine beta-Synthase) SB - IM MH - Acyl Coenzyme A/*metabolism MH - Animals MH - Cholesterol Esters/*metabolism MH - CpG Islands MH - Cystathionine beta-Synthase/genetics/metabolism MH - Diet MH - Folic Acid Deficiency/metabolism MH - Homocysteine/*blood MH - Hyperhomocysteinemia/blood/genetics/*metabolism MH - Lipid Metabolism MH - Liver/*metabolism MH - Methionine/administration & dosage/metabolism/pharmacology MH - Methylation MH - Mice MH - Mice, Inbred C57BL MH - Oleic Acid/*metabolism MH - RNA, Messenger/metabolism MH - Sterol O-Acyltransferase/genetics/*metabolism MH - Sterol O-Acyltransferase 2 EDAT- 2009/12/19 06:00 MHDA- 2010/02/05 06:00 CRDT- 2009/12/19 06:00 PHST- 2009/12/19 06:00 [entrez] PHST- 2009/12/19 06:00 [pubmed] PHST- 2010/02/05 06:00 [medline] AID - S0022-3166(22)06953-X [pii] AID - 10.3945/jn.109.112920 [doi] PST - ppublish SO - J Nutr. 2010 Feb;140(2):231-7. doi: 10.3945/jn.109.112920. Epub 2009 Dec 16.