Triggers and mechanisms of skeletal muscle wasting in chronic obstructive pulmonary disease

Abstract

Skeletal muscle wasting contributes to impaired exercise capacity, reduced health-related quality of life and is an independent determinant of mortality in chronic obstructive pulmonary disease. An imbalance between protein synthesis and myogenesis on the one hand, and muscle proteolysis and apoptosis on the other hand, has been proposed to underlie muscle wasting in this disease. In this review, the current understanding of the state and regulation of these processes governing muscle mass in this condition is presented. In addition, a conceptual mode of action of disease-related determinants of muscle wasting including disuse, hypoxemia, malnutrition, inflammation and glucocorticoids is provided by overlaying the available associative clinical data with causal evidence, mostly derived from experimental models. Significant progression has been made in understanding and managing muscle wasting in chronic obstructive pulmonary disease. Further examination of the time course of muscle wasting and specific disease phenotypes, as well as the application of systems biology and omics approaches in future research will allow the development of tailored strategies to prevent or reverse muscle wasting in chronic obstructive pulmonary disease. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

Keywords: 4E-BP1; 4E-binding protein-1; AA; ALS; AMPK; C-reactive protein; COPD; CRP; ERK; FFM; FOXO; GC; GR; GR DNA binding element; GRE; GSK3β; HIF1α; HPA axis; IGF-1; IL; IRS-1; JNK; MAFbx; MAPK; MuRF1; Muscle atrophy; Myogenesis; NF-κB; Nedd4; P70S6K; PARP; PI-3K; Protein synthesis; Proteolysis; REDD1; REE; STAT; TGF; TLR; TNF-α; TSC2; TWEAK; Toll-like receptor; UPS; Ub; adenosine monophosphate-activated protein kinase; amino acid; autophagy-lysosomal system; c-Jun N-terminal kinase; chronic obstructive pulmonary disease; extracellular signal regulated kinase; fat-free mass; forkhead box O; glucocorticoid; glucocorticoid receptor; glycogen synthase kinase 3β; hypothalamic-pituitary-adrenal axis; hypoxia inducible factor 1α; insulin receptor substrate-1; insulin-like growth factor-1; interleukin; mTOR; mammalian target of rapamycin; mitogen activated protein kinase; muscle RING finger protein; muscle atrophy F-box; neural precursor cell expressed developmentally down-regulated protein 4; nuclear Factor kappa-light-chain-enhancer of activated B cells; p70S6-kinase; phosphatidylinositol-4,5-bisphosphate 3-kinase; poly ADP ribose polymerase; regulated in development and DNA damage responses-1; resting energy expenditure; signal transducer and activator of transcription; transforming growth factor; tuberous suppressor complex 2; tumor necrosis factor-alpha; tumor necrosis factor-like weak inducer of apoptosis; ubiquitin; ubiquitin 26S-proteasome system.