Growth differentiation factor-15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo

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Title: Growth differentiation factor-15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo
Authors: Patel, MS
Lee, J
Baz, M
Wells, CE
Bloch, S
Lewis, A
Donaldson, AV
Garfield, B
Hopkinson, NS
Natanek, SA
Man, W
Wells, D
Baker, EH
Polkey, MI
Kemp, P
Item Type: Journal Article
Abstract: Background Loss of muscle mass is a co-morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor-15 (GDF-15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF-15 may contribute to muscle wasting in COPD. Methods We determined the expression of GDF-15 in the serum and muscle of patients with COPD and analysed the association of GDF-15 expression with muscle mass and exercise performance. To determine whether GDF-15 had a direct effect on muscle, we also determined the effect of increased GDF-15 expression on the tibialis anterior of mice by electroporation. Results Growth differentiation factor-15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF-15 was inversely correlated with rectus femoris cross-sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF-15 levels were associated with 8-oxo-dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over-expression of GDF-15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF-15 on muscle mass (P < 0.001). Conclusions Together, the data suggest that GDF-15 contributes to the loss of muscle mass in COPD.
Issue Date: 29-Dec-2015
Date of Acceptance: 2-Nov-2015
URI: http://hdl.handle.net/10044/1/29199
DOI: https://dx.doi.org/10.1002/jcsm.12096
ISSN: 2190-6009
Publisher: Springer Verlag (Germany)
Start Page: 436
End Page: 448
Journal / Book Title: Journal of Cachexia, Sarcopenia and Muscle
Volume: 7
Issue: 4
Copyright Statement: © 2015 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting Disorders This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: National Institute for Health Research
Medical Research Council (MRC)
AstraZeneca UK Limited
Royal Brompton & Harefield NHS Foundation Trust
Funder's Grant Number: BRU 6535
97159 (MRC ref G1001362)
Paul Kemp 6101
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Keywords: Atrophy
COPD
Electroporation
GDF‐15
Muscle mass
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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