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

Kneppers, Anita; Langen, Ramon; Gosker, Harry R.; Verdijk, Lex B.; Lipovec, Nanca Cebron; Leermakers, Pieter A.; Kelders, Marco; Theije, Chiel C. de; Omersa, Daniel; Lainščak, Mitja; Schols, A.M.W.J.

doi:10.1016/j.jamda.2017.04.016

Cited by 43 publications

(50 citation statements)

References 51 publications

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“…1,2,29,[32][33][34][37][38][39] Those studies utilized different cut-off points and methods to identify LMM, LMS, and LPP. Muscle mass was measured by dual-energy X-ray absorptiometry (sixteen studies), 13,21,22,[24][25][26]28,[33][34][35][36][37][38]40 bioelectrical impedance analysis (six studies), 1,2,23,27,31,32,39 and calf circumference (one study). 29 Muscle strength was measured via handgrip dynamometry (seven studies).…”

Section: Methods Used To Assess Sarcopeniamentioning

confidence: 99%

Diagnosis, prevalence, and clinical impact of sarcopenia in COPD: a systematic review and meta‐analysis

Sepúlveda-Loyola

Osadnik

Phu

et al. 2020

J cachexia sarcopenia muscle

139

109

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Sarcopenia prevalence and its clinical impact are reportedly variable in chronic obstructive pulmonary disease (COPD) due partly to definition criteria. This review aimed to identify the criteria used to diagnose sarcopenia and the prevalence and impact of sarcopenia on health outcomes in people with COPD. This review was registered in PROSPERO (CRD42018092576). Five electronic databases were searched to August 2018 to identify studies related to sarcopenia and COPD. Study quality was assessed using validated instruments matched to study designs. Sarcopenia prevalence was determined using authors' definitions. Comparisons were made between people who did and did not have sarcopenia for pulmonary function, exercise capacity, quality of life, muscle strength, gait speed, physical activity levels, inflammation/oxidative stress, and mortality. Twenty-three studies (70% cross-sectional) from Europe (10), Asia (9), and North and South America (4) involving 9637 participants aged ≥40 years were included (69.5% men). Sarcopenia criteria were typically concordant with recommendations of hEuropean and Asian consensus bodies. Overall sarcopenia prevalence varied from 15.5% [95% confidence interval (CI) 11.8-19.1; combined muscle mass, strength, and/or physical performance criteria] to 34% (95%CI 20.6-47.3; muscle mass criteria alone) (P = 0.009 between subgroups) and was greater in people with more severe [37.6% (95%CI 24.8-50.4)] versus less severe [19.1% (95%CI 10.2-28.0)] lung disease (P = 0.020), but similar between men [41.0% (95%CI 26.2-55.9%)] and women [31.9% (95%CI 7.0-56.8%)] (P = 0.538). People with sarcopenia had lower predicted forced expiratory volume in the first second (mean difference À7.1%; 95%CI À9.0 to À5.1%) and poorer exercise tolerance (standardized mean difference À0.8; 95%CI À1.4 to À0.2) and quality of life (standardized mean difference 0.26; 95%CI 0.2-0.4) compared with those who did not (P < 0.001 for all). No clear relationship was observed between sarcopenia and inflammatory or oxidative stress biomarkers. Incident mortality was unreported in the literature. Sarcopenia is prevalent in a significant proportion of people with COPD and negatively impacts upon important clinical outcomes. Opportunities exist to optimize its early detection and management and to evaluate its impact on mortality in this patient group.

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Section: Methods Used To Assess Sarcopeniamentioning

confidence: 99%

Diagnosis, prevalence, and clinical impact of sarcopenia in COPD: a systematic review and meta‐analysis

Sepúlveda-Loyola

Osadnik

Phu

et al. 2020

J cachexia sarcopenia muscle

139

109

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“…FOXO3 was also identified in a network-based analysis comparing serum proteomics in patients with Duchenne muscular dystrophy and age-matched controls 28 , suggesting potential for FOXO3 as a protein biomarker to monitor disease progression in conditions with severe skeletal muscle atrophy. Patients with chronic obstructive pulmonary disease displayed an increased ratio of phosphorylated FOXO3 to total FOXO3 in their muscle when compared with healthy controls with or without sarcopenia 29 .…”

Section: Foxo3 and The Regulation Of Skeletal Muscle Homeostasismentioning

confidence: 96%

Recent advances in understanding the role of FOXO3

et al. 2018

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The forkhead box O3 (FOXO3, or FKHRL1) protein is a member of the FOXO subclass of transcription factors. FOXO proteins were originally identified as regulators of insulin-related genes; however, they are now established regulators of genes involved in vital biological processes, including substrate metabolism, protein turnover, cell survival, and cell death. FOXO3 is one of the rare genes that have been consistently linked to longevity in in vivo models. This review provides an update of the most recent research pertaining to the role of FOXO3 in (i) the regulation of protein turnover in skeletal muscle, the largest protein pool of the body, and (ii) the genetic basis of longevity. Finally, it examines (iii) the role of microRNAs in the regulation of FOXO3 and its impact on the regulation of the cell cycle.

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“…Similarly, the exercise response in COPD patients may be limited by impaired satellite cell mediated skeletal muscle regeneration . Furthermore, we recently showed an elevated basal activity of skeletal muscle remodelling‐related processes in COPD patients . This may hinder the normal induction of these processes during skeletal muscle recovery after disuse or upon exercise training …”

Section: Introductionmentioning

confidence: 99%

“…14 Furthermore, we recently showed an elevated basal activity of skeletal muscle remodelling-related processes in COPD patients. 15 This may hinder the normal induction of these processes during skeletal muscle recovery after disuse or upon exercise training. 12 Several studies assessed molecular markers of remodellingrelated processes upon exercise training in COPD patients, 16,17,10,18 but none report a clear differential rehabilitation response between predefined phenotypic categories, for example, based on body composition.…”

Section: Introductionmentioning

confidence: 99%

Distinct skeletal muscle molecular responses to pulmonary rehabilitation in chronic obstructive pulmonary disease: a cluster analysis

Kneppers

Haast

Langen

et al. 2019

J cachexia sarcopenia muscle

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Background Pulmonary rehabilitation (PR) is a cornerstone in the management of chronic obstructive pulmonary disease (COPD), targeting skeletal muscle to improve functional performance. However, there is substantial inter‐individual variability in the effect of PR on functional performance, which cannot be fully accounted for by generic phenotypic factors. We performed an unbiased integrative analysis of the skeletal muscle molecular responses to PR in COPD patients and comprehensively characterized their baseline pulmonary and physical function, body composition, blood profile, comorbidities, and medication use. Methods Musculus vastus lateralis biopsies were obtained from 51 COPD patients (age 64 ± 1 years, sex 73% men, FEV 1 , 34 (26–41) %pred.) before and after 4 weeks high‐intensity supervised in‐patient PR. Muscle molecular markers were grouped by network‐constrained clustering, and their relative changes in expression values—assessed by qPCR and western blot—were reduced to process scores by principal component analysis. Patients were subsequently clustered based on these process scores. Pre‐PR and post‐PR functional performance was assessed by incremental cycle ergometry and 6 min walking test (6MWT). Results Eight molecular processes were discerned by network‐constrained hierarchical clustering of the skeletal muscle molecular rehabilitation responses. Based on the resulting process scores, four clusters of patients were identified by hierarchical cluster analysis. Two major patient clusters differed in PR‐induced autophagy ( P < 0.001), myogenesis ( P = 0.014), glucocorticoid signalling ( P < 0.001), and oxidative metabolism regulation ( P < 0.001), with Cluster 1 (C1; n = 29) overall displaying a more pronounced change in marker expression than Cluster 2 (C2; n = 16). General baseline characteristics did not differ between clusters. Following PR, both 6 min walking distance (+26.5 ± 8.3 m, P = 0.003) and peak load on the cycle ergometer test (+9.7 ± 1.9 W, P < 0.001) were improved. However, the functional improvement was more pronounced in C1, as a higher percentage of patients exceeded the minimal clinically important difference in peak workload (61 vs. 21%, P = 0.022) and both peak workload and 6 min walking test (52 vs. 8%, P = 0.008) upon PR. Conclusions We identified patient groups with distinct skeletal muscle molecular responses to rehabilitation, associated with differences in functional improvements upon PR.

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

Abstract: 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.

Cited by 43 publications

References 51 publications

Diagnosis, prevalence, and clinical impact of sarcopenia in COPD: a systematic review and meta‐analysis

Diagnosis, prevalence, and clinical impact of sarcopenia in COPD: a systematic review and meta‐analysis

Recent advances in understanding the role of FOXO3

Distinct skeletal muscle molecular responses to pulmonary rehabilitation in chronic obstructive pulmonary disease: a cluster analysis

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