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

Authors :
Michaela Krupková
František Liška
Olena Oliyarnyk
Lucie Šedová
Ondřej Šeda
Ludmila Kazdova
Drahomíra Křenová
Blanka Chylíková
Vladimír Křen
Source :
Scopus-Elsevier, Lipids in Health and Disease

Abstract

Background Several members of connexin family of transmembrane proteins were previously implicated in distinct metabolic conditions. In this study we aimed to determine the effects of complete and heterozygous form of connexin50 gene (Gja8) mutation L7Q on metabolic profile and oxidative stress parameters in spontaneously hypertensive inbred rat strain (SHR). Methods Adult, standard chow-fed male rats of SHR, heterozygous SHR-Dca+/− and SHR-Dca−/− coisogenic strains were used. At the age of 4 months, dexamethasone (2.6 μg/ml) was administered in the drinking water for three days. The lipidemic profile (cholesterol and triacylglycerol concentration in 20 lipoprotein fractions, chylomicron, VLDL, LDL and HDL particle sizes) together with 33 cytokines and hormones in serum and several oxidative stress parameters in plasma, liver, kidney and heart were assessed. Results SHR and SHR-Dca−/− rats had similar concentrations of triacylglycerols and cholesterol in all major lipoprotein fractions. The heterozygotes reached significantly highest levels of total (SHR-Dca+/−: 51.3 ± 7.2 vs. SHR: 34.5 ± 2.4 and SHR-Dca−/−: 34.4 ± 2.5 mg/dl, p = 0.026), chylomicron and VLDL triacylglycerols. The heterozygotes showed significantly lowest values of HDL cholesterol (40.9 ± 2.3 mg/dl) compared both to SHR (51.8 ± 2.2 mg/dl) and SHR-Dca−/− (48.6 ± 2.7 mg/dl). Total and LDL cholesterol in SHR-Dca+/− was lower compared to SHR. Glucose tolerance was improved and insulin concentrations were lowest in SHR-Dca−/− (1.11 ± 0.20 pg/ml) in comparison with both SHR (2.32 ± 0.49 pg/ml) and SHR-Dca+/− (3.04 ± 0.21 pg/ml). The heterozygous rats showed profile suggestive of increased oxidative stress as well as highest serum concentrations of several pro-inflammatory cytokines including interleukins 6, 12, 17, 18 and tumor necrosis factor alpha. Conclusions Our results demonstrate that connexin50 mutation in heterozygous state affects significantly the lipid profile and the oxidative stress parameters in the spontaneously hypertensive rat strain. Electronic supplementary material The online version of this article (doi:10.1186/s12944-016-0376-3) contains supplementary material, which is available to authorized users.

Details

Database :
OpenAIRE
Journal :
Scopus-Elsevier, Lipids in Health and Disease
Accession number :
edsair.doi.dedup.....007b7f1b63acb2ecaff708e59c5976fc