Pharmacogenetic interaction between dexamethasone and Cd36-deficient segment of spontaneously hypertensive rat chromosome 4 affects triacylglycerol and cholesterol distribution into lipoprotein fractions
Abstract
Dexamethasone (DEX) is known to induce diabetes and dyslipidemia. We have compared fasting triacylglycerol and cholesterol (CH) concentrations across 20 lipoprotein fractions and glucose tolerance in control and DEX-treated male Brown Norway (BN) and congenic BN.SHR-(Il6-Cd36)/Cub (BN.SHR4) rats, which differs from BN in a chromosome 4 segment including a mutant Cd36 gene, a known target of DEX.
Compared to BN, the standard-diet-fed BN.SHR4 showed higher CH and triacylglycerol concentrations, particularly in small VLDL and LDL particles. Total CH was decreased by DEX by more than 21% in BN.SHR4 but not changed in BN (strain*DEX interaction p = 0.0017).
Also, 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 and DEX-induced glucose intolerance and triacylglycerol and CH redistribution into lipoprotein fractions.