Nutritional modulation of skeletal muscle weakness in an experimental model of repetitive COPD exacerbations

<h2>Abstract</h2><h3>Background</h3> Skeletal muscle weakness is a major extra-pulmonary manifestation in chronic obstructive pulmonary disease (COPD), hallmarked by loss of skeletal muscle mass and mitochondrial function. Disease-related triggers, such as systemic inflammation, malnutrition and low physical activity levels, converge and intensify during acute exacerbations (AECOPDs). The resulting accelerated muscle deterioration in turn increases the risk of (recurrent) AECOPD, causing a vicious circle of deterioration. Targeted multi-nutrient supplementation may counteract AECOPD-induced muscle weakness. Its effects were evaluated on muscle function and mass and gene and protein expression in an AECOPD mouse model. <h3>Methods</h3> Male C57Bl/6J mice (n = 88) were exposed to intratracheal elastase/control instillations to induce emphysema, followed by intratracheal lipopolysaccharide (LPS)/control instillations to induce transient inflammation. Nutritional supplementation including N-3 LCPUFAs, vitamin D, tryptophan and prebiotic fibres was applied from the first LPS instillation onwards. Outcomes included body weight, muscle weight and function and protein and gene expression levels of markers reflecting muscle protein and mitochondrial turnover. <h3>Results</h3> Body weight, muscle mass and muscle function were decreased in LPS and elastase + LPS exposed mice. Mitophagy and mitochondrial biogenesis signalling were increased in elastase + LPS exposed mice. Protein synthesis was downregulated, while no effect on proteolysis was observed. Nutritional supplementation prevented loss of muscle weight, possibly caused by attenuating the decrease in protein synthesis and had no effect on mitochondrial expression. <h3>Conclusion</h3> The current experimental repetitive AECOPD model induces loss of muscle mass and function, without affecting mitochondrial expression. Targeted multi-nutrient supplementation during AECOPDs poses new treatment options to prevent or decelerate AECOPD-induced muscle wasting.