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Effects of mtDNA in SHR-mtF344 versus SHR conplastic strains on reduced OXPHOS enzyme levels, insulin resistance, cardiac hypertrophy, and systolic dysfunction
- Source :
- Physiological Genomics. 46:671-678
- Publication Year :
- 2014
- Publisher :
- American Physiological Society, 2014.
-
Abstract
- 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-mtF344 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-mtF344 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.
- Subjects :
- Male
medicine.medical_specialty
Mitochondrial DNA
Systole
Physiology
Molecular Sequence Data
Gene Dosage
Blood Pressure
Cardiomegaly
Mitochondrion
Biology
DNA, Mitochondrial
Oxidative Phosphorylation
Ventricular Function, Left
Electron Transport
Electrocardiography
Insulin resistance
Spontaneously hypertensive rat
RNA, Transfer
Inbred strain
Rats, Inbred SHR
Internal medicine
Diabetes mellitus
Genetics
medicine
Animals
Insulin
Base Sequence
Adenine Nucleotides
Haplotype
Organ Size
Sequence Analysis, DNA
Glucose Tolerance Test
Lipid Metabolism
medicine.disease
Rats, Inbred F344
Laboratory rat
Genes, Mitochondrial
Glucose
Phenotype
Endocrinology
Haplotypes
Insulin Resistance
Subjects
Details
- ISSN :
- 15312267 and 10948341
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Physiological Genomics
- Accession number :
- edsair.doi.dedup.....86dfb544019a5ece8b0e9ddf27832058
- Full Text :
- https://doi.org/10.1152/physiolgenomics.00069.2014