ArticleThe Journal of physiology2012
Pharmacological activation of the pyruvate dehydrogenase complex reduces statin-mediated upregulation of FOXO gene targets and protects against statin myopathy in rodents.
Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Statins promote muscle metabolic danger and NLRP3-mediated myopathy via lower protein-prenylation and YAP.Science advances · 2026Article
- Simvastatin modulates osteogenic differentiation in Stem Cells isolated from Apical Papilla.BMC oral health · 2025Article
- Distinct Impact of Doxorubicin on Skeletal Muscle and Fat Metabolism in Mice: Without Dexrazoxane Effect.International journal of molecular sciences · 2025Article
- An in vitro model to study molecular pathogenesis of sarcopenia established by a SASP-dependent human myotube culture.PloS one · 2025Article
- Pyruvate dehydrogenase kinase 4 promotes ubiquitin-proteasome system-dependent muscle atrophy.Journal of cachexia, sarcopenia and muscle · 2022Article
- Molecular Mechanisms of Muscle Fatigue.International journal of molecular sciences · 2021Review
- Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications.Bioscience reports · 2021Review
- PPARδ and FOXO1 Mediate Palmitate-Induced Inhibition of Muscle Pyruvate Dehydrogenase Complex and CHO Oxidation, Events Reversed by Electrical Pulse Stimulation.International journal of molecular sciences · 2020Article
- Regulation of lactate production through p53/β-enolase axis contributes to statin-associated muscle symptoms.EBioMedicine · 2019Article
- PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Statins, Muscle Disease and Mitochondria.Journal of clinical medicine · 2017Review
- Risk of Myopathy in Patients in Therapy with Statins: Identification of Biological Markers in a Pilot Study.Frontiers in pharmacology · 2017Article
- L-Carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin in ovariectomized rats.Journal of Zhejiang University. Science. B · 2016Article
- A metabolic switch toward lipid use in glycolytic muscle is an early pathologic event in a mouse model of amyotrophic lateral sclerosis.EMBO molecular medicine · 2015Article
- Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.European heart journal · 2015Review
- Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression.The Journal of physiology · 2015Article
- A Genome-Wide mRNA Screen and Functional Analysis Reveal FOXO3 as a Candidate Gene for Chicken Growth.PloS one · 2015Article
- Statin-Induced Increases in Atrophy Gene Expression Occur Independently of Changes in PGC1α Protein and Mitochondrial Content.PloS one · 2015Article
- Statin-induced Myopathy in Skeletal Muscle: the Role of Exercise.Journal of lifestyle medicine · 2014Review
- The role of pyruvate dehydrogenase kinase in diabetes and obesity.Diabetes & metabolism journal · 2014Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
We previously reported that statin myopathy is associated with impaired carbohydrate (CHO) oxidation in fast-twitch rodent skeletal muscle, which we hypothesised occurred as a result of forkhead box protein O1 (FOXO1) mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) gene transcription. Upregulation of FOXO gene targets known to regulate proteasomal and lysosomal muscle protein breakdown was also evident. We hypothesised that increasing CHO oxidation in vivo, using the pyruvate dehydrogenase complex (PDC) activator, dichloroacetate (DCA), would blunt activation of FOXO gene targets and reduce statin myopathy. Female Wistar Hanover rats were dosed daily for 12 days (oral gavage) with either vehicle (control, 0.5% w/v hydroxypropyl-methylcellulose 0.1% w/v polysorbate-80; n = 9), 88 mg( )kg(-1) day(-1) simvastatin (n = 8), 88 mg( )kg(-1) day(-1) simvastatin + 30 mg kg(-1) day(-1) DCA (n = 9) or 88 mg kg(-1) day(-1) simvastatin + 40 mg kg(-1) day(-1) DCA (n = 9). Compared with control, simvastatin reduced body mass gain and food intake, increased muscle fibre necrosis, plasma creatine kinase levels, muscle PDK4, muscle atrophy F-box (MAFbx) and cathepsin-L mRNA expression, increased PDK4 protein expression, and proteasome and cathepsin-L activity, and reduced muscle PDC activity. Simvastatin with DCA maintained body mass gain and food intake, abrogated the myopathy, decreased muscle PDK4 mRNA and protein, MAFbx and cathepsin-L mRNA, increased activity of PDC and reduced proteasome activity compared with simvastatin. PDC activation abolished statin myopathy in rodent skeletal muscle, which occurred at least in part via inhibition of FOXO-mediated transcription of genes regulating muscle CHO utilisation and protein breakdown.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.