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

O’Leary, Mary F.; Wallace, Graham R.; Davis, Edward T.; Murphy, David P.; Nicholson, Thomas; Bennett, Andrew J.; Tsintzas, Kostas; Jones, Simon W.

Authors

Mary F. O’Leary

Graham R. Wallace

Edward T. Davis

David P. Murphy

Thomas Nicholson

Simon W. Jones



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.

Journal Article Type Article
Publication Date 2018-12
Journal Scientific Reports (Deleted)
Print ISSN 2045-2322
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 8
Issue 1
Article Number 15360
APA6 Citation O’Leary, M. F., Wallace, G. R., Davis, E. T., Murphy, D. P., Nicholson, T., Bennett, A. J., …Jones, S. W. (2018). Obese subcutaneous adipose tissue impairs human myogenesis, particularly in old skeletal muscle, via resistin-mediated activation of NFκB. Scientific Reports, 8(1), doi:10.1038/s41598-018-33840-x
DOI https://doi.org/10.1038/s41598-018-33840-x
Keywords Multidisciplinary
Publisher URL https://www.nature.com/articles/s41598-018-33840-x

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