Cholesterol Research Today is a free monthly online journal that collates and summarizes the latest research about Cholesterol, including details on high cholesterol, hdl, ldl, diet, risks. | ||||||
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Hepatic acyl-coenzyme a:cholesterol acyltransferase-2 expression is decreased in mice with hyperhomocysteinemia.Devlin AM, Singh R, Bottiglieri T, Innis SM, Green TJ Department of Pathology and Laboratory Medicine, Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver V5Z 4H4, Canada. angela.devlin@ubc.ca 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. Published 21 January 2010 in J Nutr, 140(2): 231-7. Articles on Cholesterol published 20 January 2010: Changes in cholesterol biosynthetic and transport pathways after excitotoxicity. J Neurochem, 112(1): 34-41. The present study was carried out to elucidate changes in the gene expression and activity of cholesterol biosynthetic enzymes and transporters in the rat hippocampus after kainate excitotoxicity. Significantly increased cholesterol level was detected in the degenerating hippocampus, reaching double normal levels at 1 week after kainate injury. RT-PCR analyses of hippocampal homogenates showed significantly decreased mRNA expression of the transcription factor controlling cholesterol ... [Abstract] [Full-text] Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain. J Neurochem, 112(1): 193-203. Cathepsin D (CTSD) deficiencies are fatal neurological diseases that in human infants and in sheep are characterized by extreme loss of neurons and myelin. To date, similar morphological evidence for myelin disruption in CTSD knockout mice has not been reported. Here, we show that CTSD deficiency leads to pronounced myelin changes in the murine brain: myelin-related proteolipid protein and myelin basic protein were both markedly reduced at postnatal day 24, and the amount of lipids ... [Abstract] [Full-text] Articles on Cholesterol published 28 December 2009: Characterization of a carbon-carbon hydrolase from Mycobacterium tuberculosis involved in cholesterol metabolism. J Biol Chem, 285(1): 434-43. In the recently identified cholesterol catabolic pathway of Mycobacterium tuberculosis, 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase (HsaD) is proposed to catalyze the hydrolysis of a carbon-carbon bond in 4,5-9,10-diseco-3-hydroxy-5,9,17-tri-oxoandrosta-1(10),2-diene-4-oic acid (DSHA), the cholesterol meta-cleavage product (MCP) and has been implicated in the intracellular survival of the pathogen. Herein, purified HsaD demonstrated 4-33 times higher specificity for DSHA (k(cat)/K(m) = ... [Abstract] [Full-text] Articles on Cholesterol published 24 December 2009: n-3 and n-6 Polyunsaturated fatty acids suppress sterol regulatory element binding protein activity and increase flow of non-esterified cholesterol in HepG2 cells. Br J Nutr, 103(2): 161-7. The plasma lipid-lowering effect of PUFA, one of their main beneficial effects, is considered to be related to the regulation of lipid biosynthesis through transcription factors including sterol regulatory element binding proteins (SREBP). In the present study, we compared the effect of different PUFA on SREBP activity in HepG2 cells, using a sterol regulatory element-luciferase reporter construct as a probe. Supplementation with different fatty acids reduced SREBP activity in the order 20 : ... [Abstract] [Full-text] Intervention with fish oil, but not with docosahexaenoic acid, results in lower levels of hepatic soluble epoxide hydrolase with time in apoE knockout mice. Br J Nutr, 103(1): 16-24. Long-chain n-3 PUFA from fish oil protect against death from CHD but mechanisms are not well understood. Preliminary results indicate that fish oil may affect the enzyme soluble epoxide hydrolase (sEH) and influence inflammatory pathways in a time-dependent manner. In the present study male apoE knockout (Apoe-/-) mice were randomised to three dietary groups receiving a high-fat high-cholesterol diet supplemented with 2 % (w/w) high-oleic acid sunflower-seed (HOSF) oil, DHA oil or fish oil. ... [Abstract] [Full-text] Hamburger high in total, saturated and trans-fatty acids decreases HDL cholesterol and LDL particle diameter, and increases TAG, in mildly hypercholesterolaemic men. Br J Nutr, 103(1): 91-8. The consumption of high-fat hamburger enriched with SFA and trans-fatty acids may increase risk factors for coronary vascular disease, whereas hamburger enriched with MUFA may have the opposite effect. Ten mildly hypercholesterolaemic men consumed five, 114 g hamburger patties per week for two consecutive phases. Participants consumed high-SFA hamburger (MUFA:SFA = 0.95; produced from pasture-fed cattle) for 5 weeks, consumed their habitual diets for 3 weeks and then consumed high-MUFA ... [Abstract] [Full-text] Articles on Cholesterol published 23 December 2009: An experimental assessment of in silico haplotype association mapping in laboratory mice. BMC Genet, 10: 81. BACKGROUND: To assess the utility of haplotype association mapping (HAM) as a quantitative trait locus (QTL) discovery tool, we conducted HAM analyses for red blood cell count (RBC) and high density lipoprotein cholesterol (HDL) in mice. We then experimentally tested each HAM QTL using published crosses or new F2 intercrosses guided by the haplotype at the HAM peaks. RESULTS: The HAM for RBC, using 33 classic inbred lines, revealed 8 QTLs; 2 of these were true positives as shown by published ... [Abstract] [Full-text] ATP-binding cassette transporter G1 negatively regulates thymocyte and peripheral lymphocyte proliferation. J Immunol, 184(1): 173-83. Cholesterol is a key component of cell membranes and is essential for cell growth and proliferation. How the accumulation of cellular cholesterol affects lymphocyte development and function is not well understood. We demonstrate that ATP-binding cassette transporter G1 (ABCG1) regulates cholesterol homeostasis in thymocytes and peripheral CD4 T cells. Our work is the first to describe a cell type in Abcg1-deficient mice with such a robust change in cholesterol content and the expression of ... [Abstract] [Full-text] © 2004-2010 Cholesterol Research Today. All Rights Reserved. |
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