We propose to determine the clinical significance of the alterations in both liver and muscle lipid metabolism that lead to the accumulation of tissue TG in severely burned patients. We will investigate the possible role of the accumulation of tissue TG on insulin sensitivity. We will investigate the general hypothesis that the accumulation of intracellular TG in liver and muscle either directly causes insulin resistance in those tissues or serves as an indictor of the intracellular accumulation of active fatty acid products, such as diacylglycerol (DAG), which in turn disrupt insulin action. The following specific hypotheses will be investigated in severely burned patients: 1. Intracellular TG accumulates in both muscle and liver following burn injury. This is associated with progressive resistance to the action of insulin in both tissues. 2. Treatment with the beta adrenergic blocker propranolol will reduce the release of fatty acids into the blood from adipocytes, thereby lowering liver and muscle TG levels and improving insulin sensitivity in terms of both glucose and protein metabolism by reducing the rate of delivery of fatty acids. 3. Improved insulin sensitivity in muscle with propranolol treatment will be reflected by improved insulin signaling. 4. Fatty acids, or their active intracellular products (i.e., DAG), are the direct inhibitors of insulin action, rather than tissue TG itself. 5. Insulin resistance normally persists 6 months after burn injury, and plays a role in the difficulty in regaining muscle mass in recovery from severe injury. As in the acute response, we propose the insulin resistance after 6 months is related to increased tissue lipid accumulation. Principal methodological approaches will include stable isotope tracer techniques, nuclear magnetic resonance spectroscopy (MRS) and glycogen, and measurement of the tissue levels of active products of fatty acids and key intermediates of the insulin signaling pathway. These studies will clarify the physiological and clinical significance of the alterations of tissue lipid metabolism that occur after burn injury.
| ?apek, Karel D; Culnan, Derek M; Desai, Manubhai H et al. (2018) Fifty Years of Burn Care at Shriners Hospitals for Children, Galveston. Ann Plast Surg 80:S90-S94 |
| Korkmaz-Icöz, Sevil; Szczesny, Bartosz; Marcatti, Michela et al. (2018) Olaparib protects cardiomyocytes against oxidative stress and improves graft contractility during the early phase after heart transplantation in rats. Br J Pharmacol 175:246-261 |
| Cambiaso-Daniel, Janos; Rivas, Eric; Carson, Joshua S et al. (2018) Cardiorespiratory Capacity and Strength Remain Attenuated in Children with Severe Burn Injuries at Over 3 Years Postburn. J Pediatr 192:152-158 |
| Rontoyanni, Victoria G; Malagaris, Ioannis; Herndon, David N et al. (2018) Skeletal Muscle Mitochondrial Function is Determined by Burn Severity, Sex, and Sepsis, and is Associated With Glucose Metabolism and Functional Capacity in Burned Children. Shock 50:141-148 |
| Cambiaso-Daniel, Janos; Rontoyanni, Victoria G; Foncerrada, Guillermo et al. (2018) Correlation between invasive and noninvasive blood pressure measurements in severely burned children. Burns 44:1787-1791 |
| Ojeda, Sylvia; Blumenthal, Emily; Stevens, Pamela et al. (2018) The Safety and Efficacy of Propranolol in Reducing the Hypermetabolic Response in the Pediatric Burn Population. J Burn Care Res 39:963-969 |
| Capek, Karel D; Sousse, Linda E; Hundeshagen, Gabriel et al. (2018) Contemporary Burn Survival. J Am Coll Surg 226:453-463 |
| Foncerrada, Guillermo; Culnan, Derek M; Capek, Karel D et al. (2018) Inhalation Injury in the Burned Patient. Ann Plast Surg 80:S98-S105 |
| Bohanon, Fredrick J; Nunez Lopez, Omar; Herndon, David N et al. (2018) Burn Trauma Acutely Increases the Respiratory Capacity and Function of Liver Mitochondria. Shock 49:466-473 |
| Cambiaso-Daniel, Janos; Boukovalas, Stafanos; Bitz, Genevieve H et al. (2018) Topical Antimicrobials in Burn Care: Part 1-Topical Antiseptics. Ann Plast Surg : |
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