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dc.contributor.authorWilhelmsen, A
dc.contributor.authorStephens, FB
dc.contributor.authorBennett, AJ
dc.contributor.authorKaragounis, LG
dc.contributor.authorJones, SW
dc.contributor.authorTsintzas, K
dc.date.accessioned2023-12-13T09:55:18Z
dc.date.issued2023-10-06
dc.date.updated2023-12-12T19:48:46Z
dc.description.abstractMyostatin negatively regulates skeletal muscle growth and appears upregulated in human obesity and associated with insulin resistance. However, observations are confounded by ageing, and the mechanisms responsible are unknown. The aim of this study was to delineate between the effects of excess adiposity, insulin resistance and ageing on myostatin mRNA expression in human skeletal muscle and to investigate causative factors using in vitro models. An in vivo cross-sectional analysis of human skeletal muscle was undertaken to isolate effects of excess adiposity and ageing per se on myostatin expression. In vitro studies employed human primary myotubes to investigate the potential involvement of cross-talk between subcutaneous adipose tissue (SAT) and skeletal muscle, and lipid-induced insulin resistance. Skeletal muscle myostatin mRNA expression was greater in aged adults with excess adiposity than age-matched adults with normal adiposity (2.0-fold higher; P < 0.05) and occurred concurrently with altered expression of genes involved in the maintenance of muscle mass but did not differ between younger and aged adults with normal adiposity. Neither chronic exposure to obese SAT secretome nor acute elevation of fatty acid availability (which induced insulin resistance) replicated the obesity-mediated upregulation of myostatin mRNA expression in vitro. In conclusion, skeletal muscle myostatin mRNA expression is uniquely upregulated in aged adults with excess adiposity and insulin resistance but not by ageing alone. This does not appear to be mediated by the SAT secretome or by lipid-induced insulin resistance. Thus, factors intrinsic to skeletal muscle may be responsible for the obesity-mediated upregulation of myostatin, and future work to establish causality is required.en_GB
dc.description.sponsorshipMRC Versus Arthritis Centre for Musculoskeletal Ageing Research.en_GB
dc.format.extent1-17
dc.format.mediumPrint-Electronic
dc.identifier.citationPublished online 6 October 2023en_GB
dc.identifier.doihttps://doi.org/10.1007/s11357-023-00956-6
dc.identifier.urihttp://hdl.handle.net/10871/134782
dc.identifierORCID: 0000-0001-6312-5351 (Stephens, Francis B)
dc.identifierScopusID: 12779890700 (Stephens, Francis B)
dc.language.isoenen_GB
dc.publisherSpringeren_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/37801203en_GB
dc.rights© The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.en_GB
dc.subjectAgeingen_GB
dc.subjectInsulin resistanceen_GB
dc.subjectMyostatinen_GB
dc.subjectObesityen_GB
dc.subjectPrimary human myotubesen_GB
dc.subjectSkeletal muscleen_GB
dc.titleSkeletal muscle myostatin mRNA expression is upregulated in aged human adults with excess adiposity but is not associated with insulin resistance and ageing.en_GB
dc.typeArticleen_GB
dc.date.available2023-12-13T09:55:18Z
dc.identifier.issn2509-2715
exeter.place-of-publicationSwitzerland
dc.descriptionThis is the final version. Available from Springer via the DOI in this record. en_GB
dc.identifier.eissn2509-2723
dc.identifier.journalGeroscienceen_GB
dc.relation.ispartofGeroscience
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2023-09-20
dc.rights.licenseCC BY
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2023-10-06
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2023-12-13T09:49:28Z
refterms.versionFCDVoR
refterms.dateFOA2023-12-13T09:55:51Z
refterms.panelAen_GB
refterms.dateFirstOnline2023-10-06


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© The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits
use, sharing, adaptation, distribution and reproduction in any
medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The
images or other third party material in this article are included
in the article’s Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not
included in the article’s Creative Commons licence and your
intended use is not permitted by statutory regulation or exceeds
the permitted use, you will need to obtain permission directly
from the copyright holder. To view a copy of this licence, visit
http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's licence is described as © The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.