%0 Journal Article
%T Pharmacogenetic interaction between dexamethasone and Cd36-deficient segment of spontaneously hypertensive rat chromosome 4 affects triacylglycerol and cholesterol distribution into lipoprotein fractions
%A Michaela Krupkov¨¢
%A Lucie £¿edov¨¢
%A Franti£¿ek Li£¿ka
%A Drahom¨ªra K£¿enov¨¢
%A Vladim¨ªr K£¿en
%A Ond£¿ej £¿eda
%J Lipids in Health and Disease
%D 2010
%I BioMed Central
%R 10.1186/1476-511x-9-38
%X Glucocorticoids (GC) have been utilized for decades in treatment of wide variety of inflammatory, allergic, hematological and other disorders. In spite of their demonstrated therapeutic value, glucocorticoid treatment is often accompanied with substantial side-effects, including dyslipidemia, diabetes, obesity, osteoporosis, muscle wasting, impaired wound healing or rheumatoid arthritis [1]. While the molecular mechanisms of the GC-induced metabolic disturbances have been subjected to intensive investigation [2], the genetic basis of the interindividual differences in response to GC received only limited attention so far. Several genes have been proposed to transduce or modulate the metabolic effects of glucocorticoids, including functional candidates like glucocorticoid receptor [3], 11¦Â-hydroxysteroid dehydrogenases 1 and 2 (11¦Â-HSD1, 2) [4] and corticosteroid-binding globulin (CBG) [5], and peroxisome proliferator-activated receptor alpha (PPAR¦Á) [6]. We have previously reported a comprehensive set of quantitative trait loci related to genomic architecture of metabolic syndrome including its dynamics in response to dexamethasone (DEX)-induced derangements of lipid and carbohydrate metabolism [7].In the current study, we tested the effect of deficiency of one of the DEX-target genes, fatty acid translocase Cd36 [8,9], on the DEX-induced metabolic changes. To that end, we have compared triacylglycerol and cholesterol concentrations across 20 lipoprotein fractions and glucose tolerance in control and DEX-treated adult males of two rat strains, Brown Norway (BN) and congenic BN.SHR-(Il6-Cd36)/Cub (BN.SHR4 hereafter; Rat Genome Database [10] (RGD) ID 728142). 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 into the genomic background of BN to create BN.SHR4 [11,12].All experiments were performed in agreement with the Animal Protection Law of the Cz
%U http://www.lipidworld.com/content/9/1/38