ArticlePloS one2014
Hypermethylation of Cox5a promoter is associated with mitochondrial dysfunction in skeletal muscle of high fat diet-induced insulin resistant rats.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Twin pair analysis uncovers links between DNA methylation, mitochondrial DNA quantity and obesity.Nature communications · 2025Article
- Epigenetic reprogramming of mtDNA and its etiology in mitochondrial diseases.Journal of physiology and biochemistry · 2024Review
- Article
- Aberrations in Energetic Metabolism and Stress-Related Pathways Contribute to Pathophysiology in the Neb Conditional Knockout Mouse Model of Nemaline Myopathy.The American journal of pathology · 2023Article
- COX5A Alleviates Doxorubicin-Induced Cardiotoxicity by Suppressing Oxidative Stress, Mitochondrial Dysfunction and Cardiomyocyte Apoptosis.International journal of molecular sciences · 2023Article
- Epigenetics of the Pathogenesis and Complications of Type 2 Diabetes Mellitus.TouchREVIEWS in endocrinology · 2023Review
- The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level.Frontiers in endocrinology · 2023Article
- Eggshell membrane modulates gut microbiota to prevent murine pre-cachexia through suppression of T helper cell differentiation.Journal of cachexia, sarcopenia and muscle · 2022Article
- Mitochondrial metabolism and DNA methylation: a review of the interaction between two genomes.Clinical epigenetics · 2020Review
- HMGA1-pseudogene7 transgenic mice develop B cell lymphomas.Scientific reports · 2020Article
- Imbalanced mitochondrial function provokes heterotaxy via aberrant ciliogenesis.The Journal of clinical investigation · 2019Article
- DNA methylation landscapes in the pathogenesis of type 2 diabetes mellitus.Nutrition & metabolism · 2018Review
- Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-fat diet (HFD) is an environmental factor that contributes to the pathogenesis of obesity and type 2 diabetes. A number of genes influencing oxidative phosphorylation (OXPHOS) were found to be downregulated in skeletal muscle of humans and rats treated with HFD and have been implicated in mitochondrial dysfunction, insulin resistance, and consequent type 2 diabetes. In this study, we hypothesized that DNA methylation plays a crucial role in the regulation of OXPHOS genes in skeletal muscle of rats exposed to HFD. Using whole genome promoter methylation analysis of skeletal muscle followed by qPCR and bisulfite sequencing analysis, we identified hypermethylation of Cox5a in HFD rats. Furthermore, we found that Cox5a hypermethylation was associated with downregulation of Cox5a expression at the mRNA and protein level, and a reduction in mitochondrial complex IV activity and ATP content in HFD-induced insulin resistant rats compared to controls. Moreover, we found that while exposure to palmitate resulted in hypermethylation of the Cox5a promoter in rat myotubes, demethylation with 5-aza-2'-deoxycytidine was associated with preserved Cox5a expression, as well as restoration of complex IV activity and cellular ATP content. These novel observations indicate that Cox5a hypermethylation is associated with mitochondrial dysfunction in skeletal muscle of HFD-induced insulin resistant rats.
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