Abstracts Division 3
58. Nutritional modulation of skeletal muscle weakness in an experimental model of repetitive COPD exacerbations
Lieke E.J. van Iersel1, Charlotte E. Pelgrim2, Aletta D. Kraneveld2, Ardy van Helvoort1,3, Marco C.J.M. Kelders1, Ramon C.J. Langen1, Rosanne J.H.C.G. Beijers1, Annemie M.W.J. Schols1, Harry R. Gosker1
1 Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
2 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
3 Danone Nutricia Research, Utrecht, The Netherlands
Introduction
Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) leads to reduced exercise capacity and an increased risk of morbidity and mortality. Skeletal muscle weakness is the result of loss of muscle mass as well as oxidative capacity due to mitochondrial impairment, which may be accelerated during acute exacerbations of COPD. This study aims to 1) elucidate whether repetitive acute exacerbations aggravate loss of muscle mass and oxidative capacity, and 2) whether a dietary intervention (DI) prevents muscle weakness.
Methods
C57Bl/6J male mice, aged 11-13 weeks, received three weekly intra-tracheal elastase (E) or control (C) instillations, followed by three lipopolysaccharide (LPS) or control (C) instillations. A DI or control diet (CD) was consumed for 30 days. Body weight and forelimb grip strength were monitored. Changes in gene expression of molecular markers involved in mitochondrial biogenesis, degradation, content and muscle proteolysis were determined in muscle tissue (soleus).
Results
Significant loss of body (-10.5%, p<0.0001) and muscle (-9.2%, p=0.0343) weight was observed in E+LPS versus C. The DI restored muscle weight, but not body weight. Muscle function tended to be reduced in E+LPS versus C (-8.2%, p=0.0562), without an effect of DI. No significant decrease was present in gene expression of mitochondrial biogenesis regulators and components, whereas Tfam (1.5-fold, p=0.0001) and OXPHOS complex III (1.3-fold, p=0.0309) were even upregulated in E+LPS versus C. Only PGC-1β was significantly upregulated by DI (E+LPS+CD vs. E+LPS+ID, 1.2-fold, p=0.0083). Bnip3 (1.3-fold, p=0.0192) was the only mitochondrial degradation marker significantly increased in E+LPS versus C, which was attenuated by DI. No significant changes were found for muscle proteolysis markers.
Conclusion
Recurrent exacerbations of COPD in mice result in loss of muscle mass and function. The DI was able to prevent loss of muscle mass. Protein expression data (in progress) is required to verify gene expression levels.
NUTRIM | School of Nutrition and Translational Research in Metabolism
NUTRIM aims to contribute to health maintenance and personalised medicine by unraveling lifestyle and disease-induced derangements in metabolism and by developing targeted nutritional, exercise and drug interventions. This is facilitated by a state of the art research infrastructure and close interaction between scientists, clinicians, master and PhD students.
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