All ETDs from UAB

Advisory Committee Chair

Marcus M Bamman

Advisory Committee Members

Scott Bickel

Peggy Biga

Document Type


Date of Award


Degree Name by School

Master of Science (MS) College of Arts and Sciences


The pathophysiological response to burn injuries involves severe inflammation and a hypermetabolic state, both contributing to prolonged muscle atrophy. However, the relationship between inflammation and hypermetabolism following burn injury is poorly defined. Catabolism results from energy storage depletion, in part due to futile substrate cycling, and preferentially involving amino acids. This rapid turnover of amino acids leads to massive, full body muscle wasting. The extent and duration of muscle loss is directly related to the total body surface area burned (TBSA). Severely burned patients may experience metabolic derangements and impaired muscle synthesis for up to two years. In order to characterize the role of circulating factors in skeletal muscle atrophy following burn injury, human satellite skeletal muscle cells were grown in culture and differentiated in media containing serum from burn patients or healthy, age and sex matched controls. Myotubes differentiated in burn serum demonstrated impaired myogenesis and hypertrophy. There were significant decreases in myosin content and the number of nuclei per myotube, suggesting impairments in myotube fusion as well as myotube hypertrophy. In order to determine the mechanism of impaired myogenesis, a number of proteins involved in myogenesis were studied. ADAM12, an important mediator of myotube fusion, was downregulated by incubation in burn serum. There was also evidence of an increase in IL-6 signaling, as well as decreased IL-4 signaling, suggesting an inflammatory response to burn serum as well as a decrease in growth-promoting signaling. In addition, mTOR signaling was downregulated, and this was accompanied by a decrease in total protein synthesis. In conclusion, incubation of satellite stem cells in serum from burn patients results in impaired myogenesis, indicating that circulating factors play a significant role in muscle wasting following burns. This may occur through crosstalk between inflammatory and growth-promoting signaling pathways. This study validates a novel model that will likely prove useful in delineating the humoral mechanisms of burn-induced skeletal muscle atrophy.



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