The mechanisms of cachexia underlying muscle dysfunction in COPD.

Research output: Contribution to journalArticleAcademicpeer-review

46 Citations (Scopus)

Abstract

Pulmonary cachexia is a prevalent, debilitating and well-recognized feature of COPD associated with increased mortality and loss of peripheral and respiratory muscle function. The exact cause and underlying mechanisms of cachexia in COPD are still poorly understood. Increasing evidence however shows that pathological changes in intra-cellular mechanisms of muscle mass maintenance (i.e. protein turn-over and myonuclear turn-over) are likely involved. Potential factors triggering alterations in these mechanisms in COPD include oxidative stress, myostatin and inflammation. In addition to muscle wasting, peripheral muscle in COPD is characterized by a fiber-type shift towards a more type II, glycolytic phenotype and an impaired oxidative capacity (collectively referred to as an impaired oxidative phenotype). Atrophied diaphragm muscle in COPD, however, displays an enhanced oxidative phenotype. Interestingly, intrinsic abnormalities in (lower limb) peripheral muscle seem more pronounced in either cachectic patients or weight-loss susceptible emphysema patients, suggesting that muscle wasting and intrinsic changes in peripheral muscle's oxidative phenotype are somehow intertwined. In this manuscript, we will review alterations in mechanisms of muscle mass maintenance in COPD and discuss the involvement of oxidative stress, inflammation and myostatin as potential triggers of cachexia. Moreover, we postulate that an impaired muscle oxidative phenotype in COPD can accelerate the process of cachexia, as it renders muscle in COPD less energy-efficient thereby contributing to an energy-deficit and weight loss when not dietary compensated. Furthermore, loss of peripheral muscle oxidative phenotype may increase the muscle's susceptibility to inflammation- and oxidative stress-induced muscle damage and wasting.
Original languageEnglish
Pages (from-to)1253-1262
Number of pages10
JournalJournal of Applied Physiology
Volume114
Issue number9
DOIs
Publication statusPublished - May 2013

Keywords

  • COPD
  • skeletal muscle
  • cachexia
  • energy metabolism
  • muscle mass regulation
  • OBSTRUCTIVE PULMONARY-DISEASE
  • TUMOR-NECROSIS-FACTOR
  • KAPPA-B ACTIVATION
  • VASTUS LATERALIS MUSCLE
  • BODY-MASS INDEX
  • FAT-FREE MASS
  • SKELETAL-MUSCLE
  • OXIDATIVE STRESS
  • WEIGHT-LOSS
  • FACTOR-ALPHA

Cite this