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Cellular and molecular aspects of skeletal muscle wasting in a rat model of severe burns.

Severe burned patients undergo rapid increases in metabolism (hypermetabolism) and increased energy expenditure caused by the initial inflammatory and humoral responses. These responses also elicit, on top of the bed rest period, a cascade of negative reactions leading to additional muscle wasting. Muscle wasting itself leads to insulin resistance and may have long-term health consequences. Some of these effects persist from the first few days following severe burn injury to as long as three years later after wound closing. Although insulin resistance is assumed to be triggered by several catabolic factors, an important contributor to insulin resistance is muscle wasting itself. Insulin-resistance, may eventually lead to diabetes mellitus and is a long-term complication of severe burn patients which has major implications for future morbidity and mortality. Muscle wasting is a hallmark of burns but the underlying pathophysiological pathways are not well understood. The main aim of this project is to investigate the underlying mechanisms of muscle wasting (atrophy) in a rat model of severe burns (>40% TBSA). The first part of the study will focus on the effects of severe burn trauma in rats on the metabolomic profile of skeletal muscle, liver and blood. Secondly, we will focus on the same outcome measures during muscle disuse by means of rat hindlimb suspension with or without exercise. Thirdly, immune-histochemical, Western-blotting and biochemical analysis of the skeletal muscle activation and content of satellite cells, muscle capillarisation, autophagy and/or associated metabolic signalling pathways will be done. Finally, chemical blocking of myostatin as muscle wasting regulator will be investigated. The results of this project will be linked to the results of our ongoing clinical FWO project on exercise therapy in severely burned patients.
Date:1 Oct 2019 →  Today
Disciplines:Medical intensive care, Regulation of metabolism