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J Appl Physiol (1985). 2019 Nov 27. doi: 10.1152/japplphysiol.00627.2019. [Epub ahead of print]

IL13-driven pulmonary emphysema leads to skeletal muscle dysfunction attenuated by endurance exercise.

Author information

1
Division of Pulmonary and Critical Care Medicine, Albany Medical College, United States.
2
Department of Chemistry, Hartwick College, United States.
3
Department of Molecular and Cellular Physiology, ALBANY MEDICAL COLLEGE, United States.
4
Department of Molecular and Cellular Physiology, Albany Medical College, United States.
5
Department of Neurology and Pathology, University of Pittsburgh School of Medicine, United States.
6
Department of Molecular Microbiology and Immunology, Brown University, United States.
7
Medicine, Albany Medical College, United States.

Abstract

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. While 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 show that we can use an established transgenic animal model of COPD based on inducible IL13-driven pulmonary emphysema (IL13TG) 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 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 dimensions that can be used to address specific mechanisms regulating this process.

KEYWORDS:

COPD; exercise; muscle atrophy; muscle dysfunction; pulmonary emphysema

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