Heterozygous connexin 50 mutation affects metabolic syndrome attributes in spontaneously hypertensive rat

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.

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Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

Hypertension Research ◽

10.1038/hr.2010.168 ◽

2010 ◽

Vol 34 (1) ◽

pp. 103-112 ◽

Cited By ~ 4

Author(s):

Matthias Huber ◽

Peter Heiduschka ◽

Focke Ziemssen ◽

Juliane Bolbrinker ◽

Reinhold Kreutz

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Rat Model ◽

Spontaneously Hypertensive Rat ◽

Spontaneously Hypertensive ◽

Visual Deficits ◽

Hypertensive Rat ◽

Spontaneously Hypertensive Rat Model

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Connexin 50 Mutation Lowers Blood Pressure in Spontaneously Hypertensive Rat

Physiological Research ◽

10.33549/physiolres.933432 ◽

2017 ◽

pp. 15-28 ◽

Cited By ~ 4

Author(s):

O. ŠEDA ◽

F. LIŠKA ◽

M. PRAVENEC ◽

Z. VERNEROVÁ ◽

L. KAZDOVÁ ◽

...

Keyword(s):

Blood Pressure ◽

High Density Lipoprotein ◽

High Density Lipoprotein Cholesterol ◽

Spontaneously Hypertensive Rat ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Spontaneously Hypertensive ◽

Hypertensive Rat ◽

Connexin 50

We assessed the effect of the previously uncovered gap junction protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat – dominant cataract (SHR-Dca) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR-Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR-Dca compared with SHR (P<0.01 and P<0.05, respectively; repeated measures analysis of variance (ANOVA)). With immunohistochemistry, we were able to localize Gja8 in heart, kidney, aorta, liver, and lungs, mostly in endothelium; with no differences in expression between strains. SHR-Dca rats showed decreased body weight, high-density lipoprotein cholesterol concentrations and basal insulin sensitivity in muscle. There were 21 transcripts common to the sets of 303 transcripts in kidney and 487 in heart showing >1.2-fold difference in expression between SHR and SHR-Dca. Tumor necrosis factor was the most significant upstream regulator and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR-Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR-Dca strain, decreases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney.

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