Exercise and muscle dysfunction in COPD: implications for pulmonary rehabilitation

2009 ◽  
Vol 117 (8) ◽  
pp. 281-291 ◽  
Author(s):  
William D.-C. Man ◽  
Paul Kemp ◽  
John Moxham ◽  
Michael I. Polkey
Keyword(s):  
Skeletal Muscle ◽  
Health Status ◽  
Exercise Training ◽  
Pulmonary Rehabilitation ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Pharmacological Intervention ◽  
Chronic Obstructive ◽  
Muscle Dysfunction

Skeletal muscle dysfunction in COPD (chronic obstructive pulmonary disease) patients, particularly of the quadriceps, is of clinical interest because it not only influences the symptoms that limit exercise, but may also contribute directly to poor exercise performance and health status, increased healthcare utilization, and mortality. Furthermore, unlike the largely irreversible impairment of the COPD lung, skeletal muscles represent a potential site to improve patients' level of function and quality of life. However, despite expanding knowledge of potential contributing factors and greater understanding of molecular mechanisms of muscle wasting, only one intervention has been shown to be effective in reversing COPD muscle dysfunction, namely exercise training. Pulmonary rehabilitation, an intervention based on individually tailored exercise training, has emerged as arguably the most effective non-pharmacological intervention in improving exercise capacity and health status in COPD patients. The present review describes the effects of chronic exercise training on skeletal muscles and, in particular, focuses on the known effects of pulmonary rehabilitation on the quadriceps muscle in COPD. We also describe the current methods to augment the effects of pulmonary rehabilitation and speculate how greater knowledge of the molecular pathways of skeletal muscle wasting may aid the development of novel pharmaceutical agents.

Skeletal muscle dysfunction in COPD: clinical and laboratory observations

2009 ◽  
Vol 117 (7) ◽  
pp. 251-264 ◽  
Author(s):  
William D.-C. Man ◽  
Paul Kemp ◽  
John Moxham ◽  
Michael I. Polkey
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Current Knowledge ◽  
Clinical Importance ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Skeletal Muscle Weakness ◽  
Systemic Manifestations

COPD (chronic obstructive pulmonary disease), although primarily a disease of the lungs, exhibits secondary systemic manifestations. The skeletal muscles are of particular interest because their function (or dysfunction) not only influences the symptoms that limit exercise, but may contribute directly to poor exercise performance. Furthermore, skeletal muscle weakness is of great clinical importance in COPD as it is recognized to contribute independently to poor health status, increased healthcare utilization and even mortality. The present review describes the current knowledge of the structural and functional abnormalities of skeletal muscles in COPD and the possible aetiological factors. Increasing knowledge of the molecular pathways of muscle wasting will lead to the development of new therapeutic agents and strategies to combat COPD muscle dysfunction.

scholarly journals Muscle-Bone Crosstalk in Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Lijiao Zhang ◽  
Yongchang Sun
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Skeletal Muscle ◽  
Bone Metabolism ◽  
Pulmonary Disease ◽  
Skeletal Muscles ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Endocrine Organs

Sarcopenia and osteoporosis are common musculoskeletal comorbidities of chronic obstructive pulmonary disease (COPD) that seriously affect the quality of life and prognosis of the patient. In addition to spatially mechanical interactions, muscle and bone can also serve as endocrine organs by producing myokines and osteokines to regulate muscle and bone functions, respectively. As positive and negative regulators of skeletal muscles, the myokines irisin and myostatin not only promote/inhibit the differentiation and growth of skeletal muscles, but also regulate bone metabolism. Both irisin and myostatin have been shown to be dysregulated and associated with exercise and skeletal muscle dysfunction in COPD. During exercise, skeletal muscles produce a large amount of IL-6 which acts as a myokine, exerting at least two different conflicting functions depending on physiological or pathological conditions. Remarkably, IL-6 is highly expressed in COPD, and considered to be a biomarker of systemic inflammation, which is associated with both sarcopenia and bone loss. For osteokines, receptor activator of nuclear factor kappa-B ligand (RANKL), a classical regulator of bone metabolism, was recently found to play a critical role in skeletal muscle atrophy induced by chronic cigarette smoke (CS) exposure. In this focused review, we described evidence for myokines and osteokines in the pathogenesis of skeletal muscle dysfunction/sarcopenia and osteoporosis in COPD, and proposed muscle-bone crosstalk as an important mechanism underlying the coexistence of muscle and bone diseases in COPD.

scholarly journals IL-13-driven pulmonary emphysema leads to skeletal muscle dysfunction attenuated by endurance exercise

2020 ◽  
Vol 128 (1) ◽  
pp. 134-148 ◽  
Author(s):  
Joseph Balnis ◽  
Tanner C. Korponay ◽  
Catherine E. Vincent ◽  
Diane V. Singer ◽  
Alejandro P. Adam ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Animal Model ◽  
Pulmonary Emphysema ◽  
Skeletal Muscles ◽  
Force Generation ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Generation Capacity

Patients with chronic obstructive pulmonary disease (COPD) usually develop skeletal muscle dysfunction, which represents a major comorbidity in these patients and is strongly associated with mortality and other poor outcomes. Although clinical data indicates that accelerated protein degradation and metabolic disruption are common associations of muscle dysfunction in COPD, there is very limited data on the mechanisms regulating the process, in part, due to the lack of research performed on a validated animal model of pulmonary emphysema. This model deficiency complicates the translational value of data generated with highly reductionist settings. Here, we use an established transgenic animal model of COPD based on inducible IL-13-driven pulmonary emphysema (IL-13TG) to interrogate the mechanisms of skeletal muscle dysfunction. Skeletal muscles from these emphysematous mice develop most features present in COPD patients, including atrophy, decreased oxygen consumption, and reduced force-generation capacity. Analysis of muscle proteome indicates downregulation of succinate dehydrogenase C (SDH-C), which correlates with reduced enzymatic activity, also consistent with previous clinical observations. Ontology terms identified with human data, such as ATP binding/bioenergetics are also downregulated in this animal’s skeletal muscles. Moreover, chronic exercise can partially restore muscle mass, metabolic and force-generation capacity, and SDH activity in COPD mice. We conclude that this animal model of COPD/emphysema is an adequate platform to further investigate mechanisms of muscle dysfunction in this setting and demonstrates multiple approaches that can be used to address specific mechanisms regulating this process. NEW & NOTEWORTHY Skeletal muscle dysfunction is a relevant comorbidity in patients with chronic obstructive pulmonary disease (COPD). Mechanistic research in the area has so far been accomplished with models based on specific exposures to otherwise healthy animals, and no investigation using an established and validated animal model of COPD has been accomplished. We present an animal model of COPD that was previously shown to recapitulate pulmonary functional and histologic features present in patients with COPD, and demonstrates most of the features present in patients with pulmonary emphysema-associated muscle dysfunction, which we proposed as an adequate tool to develop mechanistic research in the area.

scholarly journals Role of autophagy in sepsis-induced skeletal muscle dysfunction, whole-body metabolism, and survival

2021 ◽  
Author(s):  
Jean-Philippe Leduc-Gaudet ◽  
Kayla Miguez ◽  
Marina Cefis ◽  
Alaa Moamer ◽  
Tomer Jordi Chaffer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Skeletal Muscles ◽  
Muscle Wasting ◽  
26S Proteasome ◽  
Whole Body ◽  
Protective Mechanism ◽  
Muscle Dysfunction ◽  
Sham Operation ◽  
The Impact

Septic patients frequently develop skeletal muscle wasting and weakness, resulting in severe clinical consequences and adverse outcomes. Autophagy is a stress-induced degradative process essential to cell survival. Recent studies have demonstrated that sepsis triggers sustained induction of autophagy in skeletal muscles, although the impact of this enhanced autophagy on sepsis-induced muscle dysfunction remains unclear. Atg7 is an autophagy gene that plays a major role in autophagosome formation. Using an inducible and muscle-specific Atg7 knockout mouse model (Atg7iSkM-KO), we investigated the functional importance of skeletal muscle autophagy in sepsis. Sepsis was induced using cecal ligation and perforation (CLP) with a sham operation serving as a control. Atg7iSkM-KO mice exhibited a more severe phenotype in response to sepsis, marked by severe muscle wasting and contractile dysfunction, hypoglycemia, higher ketone levels and a decreased in survival as compared to mice with intact Atg7. Several genes that encode 26S proteasome subunits were upregulated, suggesting that activation of the ubiquitin-proteasome system is responsible for the severe muscle atrophy that was seen in these mice. Sepsis and Atg7 deletion resulted in the accumulation of mitochondrial dysfunction, although sepsis did not further worsen mitochondrial dysfunction in Atg7iSkM-KO mice. Overall, our study demonstrates that autophagy inactivation in skeletal muscles triggers significant worsening of sepsis-induced contractile and metabolic dysfunctions and negatively impacts survival. Induction of autophagy in skeletal muscles in response to sepsis thus represents a protective mechanism.

Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise

2000 ◽  
Vol 279 (4) ◽  
pp. E806-E814 ◽  
Author(s):  
Henriette Pilegaard ◽  
George A. Ordway ◽  
Bengt Saltin ◽  
P. Darrell Neufer
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Pyruvate Dehydrogenase Kinase ◽  
Heme Oxygenase 1 ◽  
Metabolic Efficiency ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels

Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60–90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to β-actin) increased by three- to sevenfold in response to exercise, peaking after 1–2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise ( n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.

Change in skeletal muscle index and its prognostic significance in conversion therapy for initially unresectable colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 56-56
Author(s):  
Hiroaki Nozawa ◽  
Shigenobu Emoto ◽  
Koji Murono ◽  
Yasutaka Shuno ◽  
Soichiro Ishihara
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscles ◽  
Systemic Chemotherapy ◽  
Stage Iv ◽  
The Body ◽  
Pharmacological Intervention ◽  
Conversion Therapy ◽  
Skeletal Muscle Index

56 Background: Systemic chemotherapy can cause loss of skeletal muscle mass in colorectal cancer (CRC) patients in the neoadjuvant and palliative settings. However, it is largely unknown how the body composition is changed by chemotherapy rendering unresectable CRC to resectable disease or how it affects the prognosis. This study aimed at elucidating the effects of systemic chemotherapy on skeletal muscles and survival in stage IV CRC patients who underwent conversion therapy. Methods: We reviewed 98 stage IV CRC patients who received systemic chemotherapy in our hospital. According to the treatment setting, patients were divided into the ‘Conversion’, ‘Neoadjuvant chemotherapy (NAC)’, and ‘Palliation’ groups. The cross-sectional area of skeletal muscles at the third lumbar level and changes in the skeletal muscle index (SMI), defined as the area divided by height squared, during chemotherapy were compared among patient groups. The effects of these parameters on prognosis were analyzed in the Conversion group. Results: The mean SMI increased by 8.0% during chemotherapy in the Conversion group (n = 38), whereas it decreased by 6.2% in the NAC group (n = 18) and 3.7% in the Palliation group (n = 42, p < 0.0001). Moreover, patients with increased SMI during chemotherapy had a better overall survival (OS) than those whose SMI decreased in the Conversion group (p = 0.021). The increase in SMI was an independent predictor of favorable OS on multivariate analysis (hazard ratio: 0.26). Conclusions: Stage IV CRC patients who underwent conversion to resection often had an increased SMI. As such an increase in SMI further conveys a survival benefit in conversion therapy, it may be important to make efforts to preserve muscle mass by meticulous approaches, such as nutritional support, muscle exercise programs, and pharmacological intervention even during chemotherapy in patients with metastatic CRC.

Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscles of STZ-induced diabetic rats

2003 ◽  
Vol 94 (6) ◽  
pp. 2433-2438 ◽  
Author(s):  
Taisuke Enoki ◽  
Yuko Yoshida ◽  
Hideo Hatta ◽  
Arend Bonen
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Skeletal Muscles ◽  
Diabetic Rats ◽  
Monocarboxylate Transporter ◽  
Sedentary Control ◽  
Monocarboxylate Transporter 1

We compared the changes in monocarboxylate transporter 1 (MCT1) and 4 (MCT4) proteins in heart and skeletal muscles in sedentary control and streptozotocin (STZ)-induced diabetic rats (3 wk) and in trained (3 wk) control and STZ-induced diabetic animals. In nondiabetic animals, training increased MCT1 in the plantaris (+51%; P < 0.01) but not in the soleus (+9%) or the heart (+14%). MCT4 was increased in the plantaris (+48%; P < 0.01) but not in the soleus muscles of trained nondiabetic animals. In sedentary diabetic animals, MCT1 was reduced in the heart (−30%), and in the plantaris (−31%; P < 0.01) and soleus (−26%) muscles. MCT4 content was also reduced in sedentary diabetic animals in the plantaris (−52%; P < 0.01) and soleus (−25%) muscles. In contrast, in trained diabetic animals, MCT1 and MCT4 in heart and/or muscle were similar to those of sedentary, nondiabetic animals ( P > 0.05) but were markedly greater than in the sedentary diabetic animals [MCT1: plantaris +63%, soleus +51%, heart +51% ( P > 0.05); MCT4: plantaris +107%, soleus +17% ( P > 0.05)]. These studies have shown that 1) with STZ-induced diabetes, MCT1 and MCT4 are reduced in skeletal muscle and/or the heart and 2) exercise training alleviated these diabetes-induced reductions.

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