Skeletal muscle myostatin mRNA expression is upregulated in aged human adults with excess adiposity but is not associated with insulin resistance and ageing

Journal article


Wilhelmsen, Andrew, Stephens, F, Bennett, Andrew J., Karagounis, Leonidas, Jones, Simon W. and Tsintzas, Kostas. (2023). Skeletal muscle myostatin mRNA expression is upregulated in aged human adults with excess adiposity but is not associated with insulin resistance and ageing. GeroScience. 46(2), pp. 2033-2049. https://doi.org/10.1007/s11357-023-00956-6
AuthorsWilhelmsen, Andrew, Stephens, F, Bennett, Andrew J., Karagounis, Leonidas, Jones, Simon W. and Tsintzas, Kostas
Abstract

Myostatin 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.

KeywordsMyostatin; Insulin resistance; Skeletal muscle; Primary human myotubes; Obesity; Ageing
Year01 Jan 2023
JournalGeroScience
Journal citation46 (2), pp. 2033-2049
PublisherSpringer
ISSN2509-2715
Digital Object Identifier (DOI)https://doi.org/10.1007/s11357-023-00956-6
Web address (URL)https://link.springer.com/article/10.1007/s11357-023-00956-6
Open accessPublished as ‘gold’ (paid) open access
Research or scholarlyResearch
Page range2033-2049
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online06 Oct 2023
Publication process dates
Accepted20 Sep 2023
Deposited19 Mar 2024
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© The Author(s) 2023.

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/.

Place of publicationSwitzerland
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