Spontaneously Hypertensive Rat Chromosome 2 with Mutant Connexin 50 Triggers Divergent Effects on Metabolic Syndrome Components.

Abstract

Metabolic syndrome is a frequent condition with multifactorial aetiology. Previous studies indicated the presence of genetic determinants of metabolic syndrome components on rat chromosome 2 (RNO2) and syntenic regions of the human genome. Our aim was to further explore these findings using novel rat models. We derived the BN-Dca and BN-Lx.Dca congenic strains by introgression of a limited RNO2 region from a spontaneously hypertensive rat strain carrying a mutation in the Gja8 gene (SHR-Dca, dominant cataract) into the genomic background of Brown Norway strain and congenic strain BN-Lx, respectively. We compared morphometric, metabolic and cytokine profiles of adult male BN-Lx, BN-Dca and BN-Lx.Dca rats. We performed in silico comparison of the DNA sequences throughout RNO2 differential segments captured in the new congenic strains. Both BN-Dca and BN-Lx.Dca showed lower total triacylglycerols and cholesterol concentrations compared to BN-Lx. Fasting insulin in BN-Dca was higher than in BN-Lx.Dca and BN-Lx. Concentrations of several proinflammatory cytokines were elevated in the BN-Dca strain, including IL-1α, IL-1β, IFN-γ and MCP-1. In silico analyses revealed over 740 DNA variants between BN-Lx and SHR genomes within the differential segment of the congenic strains. We derived new congenic models that prove that a limited genomic region of SHR-Dca RNO2 significantly affects lipid levels and insulin sensitivity in a divergent fashion.

• Authors: O Šeda, D Křenová, L Šedová, L Kazdová, M Krupková, B Chylíková, F Liška, V Křen
• Journal: Folia biologica (Folia Biol (Praha)) Vol. 63 Issue 2 Pg. 67-77 ( 2017) ISSN: 0015-5500 [Print] Czech Republic
• PMID: 28557708 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL2
• Connexins
• Interleukin-1alpha
• Interleukin-1beta
• Triglycerides
• connexin 50
• Interferon-gamma
• Cholesterol

Topics

• Animals
• Chemokine CCL2 (metabolism)
• Cholesterol (metabolism)
• Chromosomes, Mammalian (genetics)
• Connexins (genetics)
• Hypertension (metabolism)
• Interferon-gamma (metabolism)
• Interleukin-1alpha (metabolism)
• Interleukin-1beta (metabolism)
• Male
• Metabolic Syndrome (genetics, metabolism)
• Mutation (genetics)
• Rats
• Triglycerides (metabolism)