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Cited by 55Muscle Physiology and DisordersNutrition and Health in AgingMuscle metabolism and nutrition

Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia

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Kneppers, Anita E.M., Langen, Ramon C.J., Gosker, Harry R., Verdijk, Lex B., Cebron Lipovec, Nanca, Leermakers, Pieter A., Kelders, Marco C.J.M., de Theije, Chiel C. +3 more·2017·Journal of the American Medical Directors Association
DOI 10.1016/j.jamda.2017.04.016
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Abstract

Background Sarcopenia was recently recognized as an independent condition by an International Classification of Diseases, Tenth Revision, Clinical Modification code, and is a frequently observed comorbidity in chronic obstructive pulmonary disease (COPD). Muscle mass is primarily dictated by the balance between protein degradation and synthesis, but their relative contribution to sarcopenia is unclear. Objective We aimed to assess potential differential molecular regulation of protein degradation and synthesis, as well as myogenesis, in the skeletal muscle of COPD patients with and without sarcopenia. Methods Muscle biopsies were obtained from the vastus lateralis muscle. Patients with COPD were clustered based on sarcopenia defined by low appendicular skeletal muscle mass index (nonsarcopenic COPD, n = 53; sarcopenic COPD, n = 39), and compared with healthy nonsarcopenic controls (n = 13). The mRNA and protein expression of regulators and mediators of ubiquitin-proteasome system (UPS), autophagy-lysosome system (autophagy), and protein synthesis were analyzed. Furthermore, mRNA expression of myogenesis markers was assessed. Results UPS signaling was unaltered, whereas indices of UPS regulation (eg, FOXO1 protein; p-FOXO3/FOXO3), autophagy signaling (eg, LC3BII/I; p-ULK1[Ser757]/ULK1), and protein synthesis signaling (eg, AKT1; p-GSK3B/GSK3B; p-4E-BP1/4E-BP1) were increased in COPD. These alterations were even more pronounced in COPD patients with sarcopenia (eg, FOXO1 protein; p-FOXO1/FOXO1; LC3BII/I; p-ULK(Ser555); p-AKT1/AKT1; AKT1; p-4E-BP1). Furthermore, myogenic signaling (eg, MYOG) was increased in COPD despite a concomitant increase of myostatin (MSTN) mRNA expression, with no difference between sarcopenic and nonsarcopenic COPD patients. Conclusion Together with elevated myogenic signaling, the increase in muscle protein turnover signaling in COPD, which is even more prominent in COPD patients with sarcopenia, reflects molecular alterations associated with muscle repair and remodeling.

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  • A significant number of studies reported an increased LC3BII/LC3BI ratio and/or LC3B lipidation in COPD quadriceps.

    “A significant number of studies reported an increased LC3BII/LC3BI ratio and/or LC3B lipidation (another marker of activation) in COPD quadriceps [123,182,183].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [183]

    The Results section reports a lower LC3BII/I ratio in sarcopenic COPD patients than in controls, with LC3BII levels unaltered. The Discussion repeats the lower-ratio finding; it does not report increased LC3B lipidation in this cohort. The paper therefore does not support the claimed increase for this cited study. (LLM, conf=0.86)

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  • Another study reported an increase in the phosphoULK1/ULK1 ratio in COPD muscle.

    “Finally, another study reported an increase in the phosphoULK1/ULK1 ratio—ULK1 is a kinase protein essential for autophagy initiation and progression [183].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [183]

    In “Progressively Increased Autophagy Signaling in COPD and Sarcopenic COPD” (Figure 4I, K), the paper reports that relative ULK1 phosphorylation—the phospho-ULK1/ULK1 ratio—was lower at Ser757 in COPD muscle and unaltered at Ser555. It reports only a trend toward higher absolute Ser555 phosphorylation in sarcopenic COPD muscle (Figure 4L), not an increased ratio. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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  • Later, the same team found an increase in Akt signaling in COPD quadriceps.

    “Later, the same team found nevertheless an increase in Akt signaling in COPD quadriceps [183].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [183]

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Cited by

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Authors
Kneppers, A. E. M., Langen, R. C. J., Gosker, H. R., Verdijk, L. B., Cebron Lipovec, N., Leermakers, P. A., Kelders, M. C. J. M., de Theije, C. C., Omersa, D., Lainscak, M., & Schols, A. M. W. J.
Affiliations
  • Maastricht University Medical Centre (NL)
  • National Institute of Public Health (SI)
Corresponding author
Schols, Annemie M.W.J.
ORCID
Venue
Journal of the American Medical Directors Association
Publisher
Elsevier BV
Published
2017-07
Volume
18
Issue
7
Pages
637.e1-637.e11
ISSN
1525-8610 (ISSN-L)
DOI
10.1016/j.jamda.2017.04.016
OpenAlex
W2620585764
Cited by
55
References
7
Citations by year
2026: 5 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 2
FWCI
2.24
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of the American Medical Directors Association (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
sarcopenia, chronic obstructive pulmonary disease, skeletal muscle, muscle protein turnover, protein synthesis, protein degradation, ubiquitin-proteasome system, autophagy-lysosome system, myogenesis, myostatin, FOXO1, FOXO3, AKT1, GSK3B, 4E-BP1, LC3B
MeSH terms
Aged, Female, Humans, Male, Middle Aged, Muscle Proteins, Muscular Atrophy, Signal Transduction, Muscle, Skeletal, Sarcopenia

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