Back to Search
Start Over
Heterozygous connexin 50 mutation affects metabolic syndrome attributes in spontaneously hypertensive rat
- 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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Very low-density lipoprotein
Heterozygote
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Mutation, Missense
Biology
Connexin
medicine.disease_cause
Connexins
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Spontaneously hypertensive rat
Endocrinology
Internal medicine
Rats, Inbred SHR
medicine
Animals
Insulin
cardiovascular diseases
Lipoprotein
Triglycerides
Biochemistry, medical
Metabolic Syndrome
medicine.diagnostic_test
Cholesterol
Research
Biochemistry (medical)
medicine.disease
Rats
Animal models
Oxidative Stress
030104 developmental biology
chemistry
cardiovascular system
Cytokines
lipids (amino acids, peptides, and proteins)
Metabolic syndrome
Lipid profile
030217 neurology & neurosurgery
Oxidative stress
Chylomicron
circulatory and respiratory physiology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Scopus-Elsevier, Lipids in Health and Disease
- Accession number :
- edsair.doi.dedup.....007b7f1b63acb2ecaff708e59c5976fc