Physiol. Genomics AJP: Endocrinology and Metabolism
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Physiol. Genomics 27: 95-102, 2006. First published July 5, 2006; doi:10.1152/physiolgenomics.00039.2006
1094-8341/06 $8.00
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Received 4 March 2006; accepted in final form 23 June 2006.
Physiological Genomics 27:95-102 (2006)
1094-8341/06 $8.00 © 2006 American Physiological Society

Novel double-congenic strain reveals effects of spontaneously hypertensive rat chromosome 2 on specific lipoprotein subfractions and adiposity

Ondrej Seda 1,2,3, Lucie Sedová 1, Frantisek Liska 1, Drahomíra Krenová 1, Vratislav Prejzek 1, Ludmila Kazdová 2, Johanne Tremblay 3, Pavel Hamet 3 and Vladimír Kren 1

1 Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles University and the General Teaching Hospital, Prague, Czech Republic
2 Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
3 Centre de Recherche, Centre Hospitalier de l'Universite de Montreal, Montreal, Canada

We have developed a new, double-congenic rat strain BN-Lx.SHR2, which carries two distinct segments of chromosome 2 introgressed from the spontaneously hypertensive rat strain (SHR) into the genetic background of congenic strain BN-Lx, which was previously shown to express variety of metabolic syndrome features. In 16-wk-old male rats of BN-Lx and BN-Lx.SHR2 strains, we compared their glucose tolerance and triacylglycerol and cholesterol concentrations in 20 lipoprotein subfractions and the lipoprotein particle sizes under conditions of feeding standard and high-sucrose diets. Introgression of two distinct SHR-derived chromosome 2 segments resulted in decreased adiposity together with aggravation of glucose intolerance in the double-congenic strain. The BN-Lx.SHR2 rats were more sensitive to sucrose-induced rise in triacylglycerolemia. Although the total cholesterol concentrations of the two strains were comparable after the standard diet and even lower in BN-Lx.SHR2 after sucrose feeding, detailed analysis revealed that under both dietary conditions, the double-congenic strain had significantly higher cholesterol concentrations in low-density lipoprotein fractions and lower high-density lipoprotein fractions. We established a new inbred model showing dyslipidemia and mild glucose intolerance without obesity, attributable to specific genomic regions. For the first time, the chromosome 2 segments of SHR origin are shown to influence other than blood pressure-related features of metabolic syndrome or to be involved in relevant nutrigenomic interactions.

BN-Lx; triacylglycerol; cholesterol; metabolic syndrome; insulin resistance; obesity; comparative genomics






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