Obese subcutaneous adipose tissue impairs human myogenesis, particularly in old skeletal muscle, via resistin-mediated activation of NFκB.

Research output: Contribution to journalArticle

Authors

  • Edward Davis
  • David P Murphy
  • Thomas Nicholson
  • Andrew J Bennett
  • Kostas Tsintzas

External organisations

  • Royal Orthopaed Hosp
  • Department of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK
  • FRAME Alternatives Laboratory, School of Life Sciences, Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham, UK
  • MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Life Sciences, Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham, UK

Abstract

Adiposity and adipokines are implicated in the loss of skeletal muscle mass with age and in several chronic disease states. The aim of this study was to determine the effects of human obese and lean subcutaneous adipose tissue secretome on myogenesis and metabolism in skeletal muscle cells derived from both young (18-30 yr) and elderly (> 65 yr) individuals. Obese subcutaneous adipose tissue secretome impaired the myogenesis of old myoblasts but not young myoblasts. Resistin was prolifically secreted by obese subcutaneous adipose tissue and impaired myotube thickness and nuclear fusion by activation of the classical NFκB pathway. Depletion of resistin from obese adipose tissue secretome restored myogenesis. Inhibition of the classical NFκB pathway protected myoblasts from the detrimental effect of resistin on myogenesis. Resistin also promoted intramyocellular lipid accumulation in myotubes and altered myotube metabolism by enhancing fatty acid oxidation and increasing myotube respiration and ATP production. In conclusion, resistin derived from human obese subcutaneous adipose tissue impairs myogenesis of human skeletal muscle, particularly older muscle, and alters muscle metabolism in developing myotubes. These findings may have important implications for the maintenance of muscle mass in older people with chronic inflammatory conditions, or older people who are obese or overweight.

Details

Original languageEnglish
Article number15360
JournalScientific Reports
Volume8
Issue number1
Publication statusPublished - 18 Oct 2018