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Overexpression of t...
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Bass, Joseph J.MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Nottingham, UK
(författare)
Overexpression of the vitamin D receptor (VIM) induces skeletal muscle hypertrophy
- Artikel/kapitelEngelska2020
Förlag, utgivningsår, omfång ...
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Elsevier,2020
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:oru-88674
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-88674URI
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https://doi.org/10.1016/j.molmet.2020.101059DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies:Medical Research Council UK (MRC) MR/J500495/1MRC-ARUK Centre for Musculoskeletal Ageing Research Physiological Society
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Objective: The Vitamin D receptor (VDR) has been positively associated with skeletal muscle mass, function and regeneration. Mechanistic studies have focused on the loss of the receptor, with in vivo whole-body knockout models demonstrating reduced myofibre size and function and impaired muscle development. To understand the mechanistic role upregulation of the VDR elicits in muscle mass/health, we studied the impact of VDR over-expression (OE) in vivo before exploring the importance of VDR expression upon muscle hypertrophy in humans.Methods: Wistar rats underwent in vivo electrotransfer (IVE) to overexpress the VDR in the Tibialis anterior (TA) muscle for 10 days, before comprehensive physiological and metabolic profiling to characterise the influence of VDR-OE on muscle protein synthesis (MPS), anabolic signalling and satellite cell activity. Stable isotope tracer (D2O) techniques were used to assess sub-fraction protein synthesis, alongside RNA-Seq analysis. Finally, human participants underwent 20 wks of resistance exercise training, with body composition and transcriptomic analysis.Results: Muscle VDR-OE yielded total protein and RNA accretion, manifesting in increased myofibre area, i.e., hypertrophy. The observed increases in MPS were associated with enhanced anabolic signalling, reflecting translational efficiency (e.g., mammalian target of rapamycin (mTOR-signalling), with no effects upon protein breakdown markers being observed. Additionally, RNA-Seq illustrated marked extracellular matrix (ECM) remodelling, while satellite cell content, markers of proliferation and associated cell-cycled related gene-sets were upregulated. Finally, induction of VDR mRNA correlated with muscle hypertrophy in humans following long-term resistance exercise type training.Conclusion: VDR-OE stimulates muscle hypertrophy ostensibly via heightened protein synthesis, translational efficiency, ribosomal expansion and upregulation of ECM remodelling-related gene-sets. Furthermore, VDR expression is a robust marker of the hypertrophic response to resistance exercise in humans. The VDR is a viable target of muscle maintenance through testable Vitamin D molecules, as active molecules and analogues. (C) 2020 The Author(s). Published by Elsevier GmbH.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Nakhuda, AsifMRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Nottingham, UK
(författare)
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Deane, Colleen S.Department of Sport and Health Sciences, University of Exeter, Exeter, UK
(författare)
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Brook, Matthew S.MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Nottingham, UK
(författare)
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Wilkinson, Daniel J.MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Nottingham, UK
(författare)
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Phillips, Bethan E.Mitochondrial Metabolism and Ageing Laboratory, Diabetes and Metabolism Division, Garvan Institute of Medical Research, Australia; School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
(författare)
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Philp, AndrewGarvan Inst Med Res, Diabet & Metab Div, Mitochondrial Metab & Ageing Lab, Sydney, NSW 2010, Australia.;Univ Birmingham, Sch Sport Exercise & Rehabil Sci, Birmingham B15 2TT, W Midlands, England.
(författare)
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Tarum, JanelleSchool of Health Sciences, Örebro University, Örebro, Sweden
(författare)
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Kadi, Fawzi,1970-Örebro universitet,Institutionen för hälsovetenskaper(Swepub:oru)fki
(författare)
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Andersen, DitteMolecular Physiology of Diabetes Laboratory, Dept. of Comparative Biomedical Sciences, Royal Veterinary College, UK
(författare)
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Garcia, Amadeo MunozInstitute of Metabolism and Systems Research, The University of Birmingham, Birmingham, UK; Department of Bio-informatics - BiGCaT, NUTRIM School of Nutrition and Metabolism in Translational Research, Maastricht University, Maastricht, the Netherlands
(författare)
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Smith, KenMRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Nottingham, UK
(författare)
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Gallagher, Iain J.Physiology, Exercise and Nutrition Research Group, Faculty of Health Sciences and Sport, University of Stirling, Stirling, UK
(författare)
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Szewczyk, Nathaniel J.MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Nottingham, UK
(författare)
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Cleasby, Mark E.Molecular Physiology of Diabetes Laboratory, Dept. of Comparative Biomedical Sciences, Royal Veterinary College, UK
(författare)
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Atherton, Philip J.MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Nottingham, UK
(författare)
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MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Nottingham, UKDepartment of Sport and Health Sciences, University of Exeter, Exeter, UK
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Molecular Metabolism: Elsevier422212-8778
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Bass, Joseph J.
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Nakhuda, Asif
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Deane, Colleen S ...
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Brook, Matthew S ...
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Wilkinson, Danie ...
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Phillips, Bethan ...
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visa fler...
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Philp, Andrew
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Tarum, Janelle
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Kadi, Fawzi, 197 ...
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Andersen, Ditte
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Garcia, Amadeo M ...
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Smith, Ken
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Gallagher, Iain ...
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Szewczyk, Nathan ...
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Cleasby, Mark E.
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Atherton, Philip ...
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Örebro universitet