Overexpression of the vitamin D receptor (VIM) induces skeletal muscle hypertrophy

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Overexpression of the vitamin D receptor (VIM) induces skeletal muscle hypertrophy

Bass, Joseph J. (författare): 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

Nakhuda, Asif (författare): 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

Deane, Colleen S. (författare): Department of Sport and Health Sciences, University of Exeter, Exeter, UK

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Brook, Matthew S. (författare): 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

Wilkinson, Daniel J. (författare): 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

Phillips, Bethan E. (författare): 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

Philp, Andrew (författare): Garvan 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.

Tarum, Janelle (författare): School of Health Sciences, Örebro University, Örebro, Sweden

Kadi, Fawzi, 1970- (författare): Örebro universitet,Institutionen för hälsovetenskaper

Andersen, Ditte (författare): Molecular Physiology of Diabetes Laboratory, Dept. of Comparative Biomedical Sciences, Royal Veterinary College, UK

Garcia, Amadeo Munoz (författare): Institute 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

Smith, Ken (författare): 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

Gallagher, Iain J. (författare): Physiology, Exercise and Nutrition Research Group, Faculty of Health Sciences and Sport, University of Stirling, Stirling, UK

Szewczyk, Nathaniel J. (författare): 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

Cleasby, Mark E. (författare): Molecular Physiology of Diabetes Laboratory, Dept. of Comparative Biomedical Sciences, Royal Veterinary College, UK

Atherton, Philip J. (författare): 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

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Elsevier, 2020
2020
Engelska.
Ingår i: Molecular Metabolism. - : Elsevier. - 2212-8778. ; 42

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://doi.org/10.1...; https://urn.kb.se/re...; https://doi.org/10.1...; visa färre...

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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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Av författaren/redakt...: Bass, Joseph J.; Nakhuda, Asif; Deane, Colleen S ...; Brook, Matthew S ...; Wilkinson, Danie ...; Phillips, Bethan ...; visa fler...; Philp, Andrew; Tarum, Janelle; Kadi, Fawzi, 197 ...; Andersen, Ditte; Garcia, Amadeo M ...; Smith, Ken; Gallagher, Iain ...; Szewczyk, Nathan ...; Cleasby, Mark E.; Atherton, Philip ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Endokrinologi oc ...

Artiklar i publikationen: Molecular Metabo ...

Av lärosätet: Örebro universitet

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Overexpression of the vitamin D receptor (VIM) induces skeletal muscle hypertrophy

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