Effects of mtDNA in SHR-mtF344 versus SHR conplastic strains on reduced OXPHOS enzyme levels, insulin resistance, cardiac hypertrophy, and systolic dysfunction
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25073601
DOI
10.1152/physiolgenomics.00069.2014
PII: physiolgenomics.00069.2014
Knihovny.cz E-resources
- Keywords
- conplastic, diabetes, heart mass, mitochondria, spontaneously hypertensive rat,
- MeSH
- Adenine Nucleotides metabolism MeSH
- Electrocardiography MeSH
- Phenotype MeSH
- Ventricular Function, Left drug effects MeSH
- Gene Dosage MeSH
- Glucose metabolism MeSH
- Glucose Tolerance Test MeSH
- Haplotypes genetics MeSH
- Insulin pharmacology MeSH
- Insulin Resistance genetics MeSH
- Cardiomegaly genetics physiopathology MeSH
- Blood Pressure drug effects MeSH
- Lipid Metabolism drug effects MeSH
- DNA, Mitochondrial genetics MeSH
- Genes, Mitochondrial MeSH
- Molecular Sequence Data MeSH
- Oxidative Phosphorylation * drug effects MeSH
- Rats, Inbred F344 MeSH
- Rats, Inbred SHR MeSH
- RNA, Transfer genetics MeSH
- Base Sequence MeSH
- Sequence Analysis, DNA MeSH
- Systole * drug effects MeSH
- Electron Transport drug effects MeSH
- Organ Size drug effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenine Nucleotides MeSH
- Glucose MeSH
- Insulin MeSH
- DNA, Mitochondrial MeSH
- RNA, Transfer MeSH
Common inbred strains of the laboratory rat can be divided into four major mitochondrial DNA (mtDNA) haplotype groups represented by the BN, F344, LEW, and SHR strains. In the current study, we investigated the metabolic and hemodynamic effects of the SHR vs. F344 mtDNA by comparing the SHR vs. SHR-mt(F344) conplastic strains that are genetically identical except for their mitochondrial genomes. Altogether 13 amino acid substitutions in protein coding genes, seven single nucleotide polymorphisms in tRNA genes, and 12 single nucleotide changes in rRNA genes were detected in F344 mtDNA compared with SHR mtDNA. Analysis of oxidative phosphorylation system (OXPHOS) in heart left ventricles (LV), muscle, and liver revealed reduced activity and content of several respiratory chain complexes in SHR-mt(F344) conplastic rats compared with the SHR strain. Lower function of OXPHOS in LV of conplastic rats was associated with significantly increased relative ventricular mass and reduced fractional shortening that was independent of blood pressure. In addition, conplastic rats exhibited reduced sensitivity of skeletal muscles to insulin action and impaired glucose tolerance. These results provide evidence that inherited alterations in mitochondrial genome, in the absence of variation in the nuclear genome and other confounding factors, predispose to insulin resistance, cardiac hypertrophy and systolic dysfunction.
Department of Laboratory Medicine University of California San Francisco California
Institute for Clinical and Experimental Medicine Prague Czech Republic; and
Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic;
References provided by Crossref.org
Haplotype variability in mitochondrial rRNA predisposes to metabolic syndrome
