Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD

Remels, Alexander; Schrauwen, Patrick; Broekhuizen, R.; Willems, Jean; Kersten, Sander; Gosker, Harry R.; Schols, A.M.W.J.

doi:10.1183/09031936.00144106

Cited by 145 publications

(119 citation statements)

References 37 publications

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“…4) [196]. reduced expression of PGC-1a [197]. Reduced PPAR-a expression is correlated with cachexia and systemic inflammation, suggesting that PPAR-a agonists, such as clofibrate and fenofibrate, may have therapeutic potential in treating the systemic features of COPD.…”

Section: Ppar Agonistsmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

European Respiratory Journal

1,465

1,113

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Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

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Section: Ppar Agonistsmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

European Respiratory Journal

1,465

1,113

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“…Physical inactivity induces several adaptive changes in skeletal muscles, including reduced proportions of type I fi bers, attenuation of oxidative enzyme capacity, regulators of mitochondrial biogenesis (PPARs and PGC-1α), fi ber atrophy, reduction of antioxidant enzyme levels and lower capillary density (Franssen et al 2002;Lawler et al 2003;Remels et al 2007). These changes, collectively known as musculoskeletal deconditioning, result in signifi cant reductions in skeletal muscle strength and endurance.…”

Section: Inactivitymentioning

confidence: 99%

Skeletal Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease

2010

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Chronic obstructive pulmonary disease (COPD) is a debilitating disease characterized by infl ammation-induced airfl ow limitation and parenchymal destruction. In addition to pulmonary manifestations, patients with COPD develop systemic problems, including skeletal muscle and other organ-specifi c dysfunctions, nutritional abnormalities, weight loss, and adverse psychological responses. Patients with COPD often complain of dyspnea on exertion, reduced exercise capacity, and develop a progressive decline in lung function with increasing age. These symptoms have been attributed to increases in the work of breathing and in impairments in gas exchange that result from airfl ow limitation and dynamic hyperinfl ation. However, there is mounting evidence to suggest that skeletal muscle dysfunction, independent of lung function, contributes signifi cantly to reduced exercise capacity and poor quality of life in these patients. Limb and ventilatory skeletal muscle dysfunction in COPD patients has been attributed to a myriad of factors, including the presence of low grade systemic infl ammatory processes, nutritional depletion, corticosteroid medications, chronic inactivity, age, hypoxemia, smoking, oxidative and nitrosative stresses, protein degradation and changes in vascular density. This review briefl y summarizes the contribution of these factors to overall skeletal muscle dysfunction in patients with COPD, with particular attention paid to the latest advances in the fi eld. Keywords: skeletal muscles, chronic obstructive pulmonary disease, diaphragm, quadriceps, fatigue, disuse, atrophy, smoking, exercise It has long been recognized that COPD is a systemic disease in which several extrapulmonary manifestations, including cachexia and skeletal muscle dysfunction, contribute to morbidity and mortality. Functionally, skeletal muscle dysfunction in COPD patients is characterized by signifi cant reduction in muscle strength and endurance. It is structurally characterized by loss of muscle mass and cross-sectional area (muscle atrophy), fi ber type distribution (reduction in the proportion of oxidative fi bers and increases in the proportion of glycolytic fi bers), oxidative metabolic capacity (attenuation of mitochondrial enzyme activities and expression) and capillary distribution (signifi cant loss of capillary density). Although disuse and inactivity are important contributors to the pathogenesis of skeletal muscle dysfunction in COPD patients, several other systemic and local factors are also involved. These include systemic infl ammation, malnutrition, corticosteroid usage, hypoxemia, aging, smoking and local factors such as the production of reactive oxygen (ROS) and nitrogen species (RNS) and enhanced protein degradation inside muscle fi bers, a result of increased activities of the proteasomal and lysosomal pathways and activation of calpains and caspases. Evidence of skeletal muscle dysfunction in patients with COPDIt has been well established that skeletal muscle function (strength and endurance) and s...

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“…26 and reductions in peroxisome proliferator-activated receptors (involved in mitochondrial biogenesis). 43 Gosker et al 21 recently confirmed that the severity of COPD is associated with reductions in the proportion of type I fibres. The aforementioned factors together with the finding that lactic acidosis occurs earlier during exercise in COPD patients compared with healthy subjects, 33 may partly explain why COPD patients fatigue quicker and experience exercise intolerance.…”

Section: Skeletal Muscle Dysfunctionmentioning

confidence: 77%

“…In addition, it was recently hypothesised that resistance training may only induce brief 5'AMP-activated protein kinase (AMPK) activation (possibly not at all), resulting in limited AMPK-dependent adaptations such as mitochondrial biogenesis. 51 With the skeletal muscle of COPD patients already exhibiting reduced mitochondrial biogenesis, oxidative enzymes and oxidative capacity, 18,43 the possibility that resistance training may exacerbate this situation requires clarification.…”

Section: Resistance Training and Molecular Adaptations In Skeletal Mumentioning

confidence: 99%

COPD: Is there evidence to support a role for resistance training in improving measurable health-related quality of life in pulmonary rehabilitation?

Semple¹,

McKune

2007

S. Afr. j. sports med.

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Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality. As such, the disease places a significant burden on health care services. Although the pathogenesis of COPD is complex, progressive airflow limitation and a chronic inflammatory response are two hallmark characteristics of the disease. In addition, systemic manifestations such as peripheral muscle dysfunction have recently received considerable attention in the literature. Pulmonary rehabilitation is an evidence-based multidisciplinary intervention that has been shown to produce clinically relevant outcomes. One important component of rehabilitation is exercise. With the majority of COPD patients presenting with muscle weakness and exercise intolerance, the inclusion of resistance training into a pulmonary rehabilitation programme would seem appropriate. Compared with other exercise/training modalities only a small number of studies have investigated the effects of resistance training in COPD patients. Although further research is required to identify the optimal mode, intensity and frequency, it appears that resistance training may prove to be a valuable intervention for COPD patients enrolled in pulmonary rehabilitation programmes.

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Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD

Cited by 145 publications

References 37 publications

Systemic manifestations and comorbidities of COPD

Systemic manifestations and comorbidities of COPD

Skeletal Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease

COPD: Is there evidence to support a role for resistance training in improving measurable health-related quality of life in pulmonary rehabilitation?

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