Pharmacogenetic interaction between dexamethasone and Cd36-deficient segment of spontaneously hypertensive rat chromosome 4 affects triacylglycerol and cholesterol distribution into lipoprotein fractions

Lipids in Health and Disease

Short Paper

Michaela Krupková¹  František Liška¹  Drahomíra Křenová¹  Lucie Šedová²  Ondřej Šeda³  Vladimír Křen⁴ 

[1] Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles, University and the General Teaching Hospital, Albertov 4, 128 00, Prague, Czech Republic;Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles, University and the General Teaching Hospital, Albertov 4, 128 00, Prague, Czech Republic;Centre de Recherche, Centre hospitalier de l'Université de Montreal (CRCHUM), Technopole Angus, 2901 Rachel E., H1W4A4, Montreal (Quebec), Canada;Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles, University and the General Teaching Hospital, Albertov 4, 128 00, Prague, Czech Republic;Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague, Czech Republic;Centre de Recherche, Centre hospitalier de l'Université de Montreal (CRCHUM), Technopole Angus, 2901 Rachel E., H1W4A4, Montreal (Quebec), Canada;Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles, University and the General Teaching Hospital, Albertov 4, 128 00, Prague, Czech Republic;Institute of Physiology and Center for Applied Genomics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague, Czech Republic;

关键词: Lipoprotein Fraction;    Brown Norway;    Triacylglycerol Concentration;    Fatty Acid Translocase;    Differential Segment;   

DOI  :  10.1186/1476-511X-9-38

 received in 2010-03-22, accepted in 2010-04-16,  发布年份 2010

来源: Springer

【 摘 要 】

Dexamethasone (DEX) is known to induce diabetes and dyslipidemia. We have compared fasting triacylglycerol and cholesterol concentrations across 20 lipoprotein fractions and glucose tolerance in control (standard diet) and DEX-treated 7-month-old males of two rat strains, Brown Norway (BN) and congenic BN.SHR-(Il6-Cd36)/Cub (BN.SHR4). These two inbred strains differ in a defined segment of chromosome 4, originally transferred from the spontaneously hypertensive rat (SHR) including the mutant Cd36 gene, a known target of DEX. Compared to BN, the standard-diet-fed BN.SHR4 showed higher cholesterol and triacylglycerol concentrations across many lipoprotein fractions, particularly in small VLDL and LDL particles. Total cholesterol was decreased by DEX by more than 21% in BN.SHR4 contrasting with the tendency to increase in BN (strain*DEX interaction p = 0.0017). Similar pattern was observed for triacylglycerol concentrations in LDL. The LDL particle size was significantly reduced by DEX in both strains. Also, while control BN and BN.SHR4 displayed comparable glycaemic profiles during oral glucose tolerance test, we observed a markedly blunted DEX induction of glucose intolerance in BN.SHR4 compared to BN. In summary, we report a pharmacogenetic interaction between limited genomic segment with mutated Cd36 gene and dexamethasone-induced glucose intolerance and triacylglycerol and cholesterol redistribution into lipoprotein fractions.

【 授权许可】

Unknown   
© Krupková et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.