Novel double-congenic strain reveals effects of spontaneously hypertensive rat chromosome 2 on specific lipoprotein subfractions and adiposity.
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.
Seda
Ondrej
O
Institute of Biology and Medical Genetics of the First Faculty of Medicine of Charles University and the General Teaching Hospital, Prague, Czech Republic.
Sedová
Lucie
L
Liska
Frantisek
F
Krenová
Drahomíra
D
Prejzek
Vratislav
V
Kazdová
Ludmila
L
Tremblay
Johanne
J
Hamet
Pavel
P
Kren
Vladimír
V
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D020296:Animals, Congenic; D002784:Cholesterol / Q000032:analysis*; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D023281:Genomics; D018149:Glucose Intolerance / Q000235:genetics; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry*; D008297:Male; D040641:Quantitative Trait Loci; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D013395:Sucrose / Q000494:pharmacology; D014280:Triglycerides / Q000032:analysis*
D008074:Lipoproteins; D014280:Triglycerides; D013395:Sucrose; D002784:Cholesterol