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Hypoxia and muscle maintenance regulation: implications for chronic respiratory disease

Theije, Chiel dea; Costes, Frédéricb,c; Langen, Ramon C.d; Pison, Christophee,f,g,h; Gosker, Harry R.d

Current Opinion in Clinical Nutrition and Metabolic Care: November 2011 - Volume 14 - Issue 6 - p 548–553
doi: 10.1097/MCO.0b013e32834b6e79
Nutrition and physiological function: Edited by Labros S. Sidossis and Annemie Schols
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Purpose of review Muscle wasting and impaired muscle oxidative metabolism are common extrapulmonary features of chronic respiratory failure (CRF) that significantly increase disease burden. This review aims to address the question whether hypoxia, an obvious consequence of this disease, actually plays a causal role in these muscle impairments.

Recent findings In experimental models, a causal role for hypoxia in muscle atrophy and metabolic impairments has clearly been shown. Although the hypoxia-inducible factors and nuclear factor kappa B are putative mediators of these hypoxia-induced alterations, their true involvement remains to be proven. Molecular signatures of disrupted regulation of muscle mass and oxidative metabolism observed in these experimental models also have been shown in muscles of patients suffering from CRF, suggestive of but not conclusive for a causal role of hypoxia. Therapies, including but not restricted to those aimed at alleviating hypoxia, have been shown to partially but not completely restore muscle mass and oxidative capacity in CRF patients, which may imply an additive effect of nutritional modulation of substrate metabolism.

Summary Although hypoxia clearly affects skeletal muscle maintenance, it remains to be confirmed whether and by which underlying molecular mechanisms hypoxia is causally involved in CRF-related muscle atrophy and impaired oxidative capacity.

aNutrim School for Nutrition, Toxicology and Metabolism, Department of Anatomy and Embryology, Maastricht University Medical Centre+, Maastricht, The Netherlands

bService de Physiologie Clinique et de l’Exercice, Hôpital Nord, CHU Saint-Etienne

cLaboratoire Physiologie de l’Exercice, EA4338 Université Jean Monnet, Saint-Etienne, France

dNutrim School for Nutrition, Toxicology and Metabolism, Department of Anatomy and Embryology, Maastricht University Medical Centre+, Maastricht, The Netherlands

eClinique de Pneumologie, CHU Grenoble

fUniversité Joseph Fourier

gInsermU1055, Grenoble

hEuropean Institute for Systems Biology & Medicine, Lyon, France

Correspondence to H.R. Gosker, Department of Respiratory Medicine, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands Tel: +31 43 3884247; e-mail: h.gosker@maastrichtuniversity.nl

© 2011 Lippincott Williams & Wilkins, Inc.