title: Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely burned adults.
abstract: Elevated metabolic rate is a hallmark of the stress response to severe burn injury. This response is mediated in part by adrenergic stress and is responsive to changes in ambient temperature. We hypothesize that uncoupling of oxidative phosphorylation in skeletal muscle mitochondria contributes to increased metabolic rate in burn survivors. Here, we determined skeletal muscle mitochondrial function in healthy and severely burned adults. Indirect calorimetry was used to estimate metabolic rate in burn patients. Quadriceps muscle biopsies were collected on two separate occasions (11 ± 5 and 21 ± 8 days postinjury) from six severely burned adults (68 ± 19% of total body surface area burned) and 12 healthy adults. Leak, coupled, and uncoupled mitochondrial respiration was determined in permeabilized myofiber bundles. Metabolic rate was significantly greater than predicted values for burn patients at both time points (P < 0.05). Skeletal muscle oxidative capacity, citrate synthase activity, a marker of mitochondrial abundance, and mitochondrial sensitivity to oligomycin were all lower in burn patients vs. controls at both time points (P < 0.05). A greater proportion of maximal mitochondrial respiration was linked to thermogenesis in burn patients compared with controls (P < 0.05). Increased metabolic rate in severely burned adults is accompanied by derangements in skeletal muscle mitochondrial function. Skeletal muscle mitochondria from burn victims are more uncoupled, indicating greater heat production within skeletal muscle. Our findings suggest that skeletal muscle mitochondrial dysfunction contributes to increased metabolic rate in burn victims.
authors: Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas; Department of Surgery, University of Texas Medical Branch, Galveston, Texas; cr2porte@utmb.edu.
authors: Craig
authors: C
authors: Porter
authors: Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas; Department of Surgery, University of Texas Medical Branch, Galveston, Texas;
authors: David N
authors: DN
authors: Herndon
authors: Arkansas Children's Nutrition Center and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors: Elisabet
authors: E
authors: Børsheim
authors: Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas; Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas;
authors: Tony
authors: T
authors: Chao
authors: Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas;
authors: Paul T
authors: PT
authors: Reidy
authors: Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas;
authors: Michael S
authors: MS
authors: Borack
authors: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, Texas; and.
authors: Blake B
authors: BB
authors: Rasmussen
authors: Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas; Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas;
authors: Maria
authors: M
authors: Chondronikola
authors: Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas; Department of Surgery, University of Texas Medical Branch, Galveston, Texas;
authors: Manish K
authors: MK
authors: Saraf
authors: Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas; Department of Surgery, University of Texas Medical Branch, Galveston, Texas; Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
authors: Labros S
authors: LS
authors: Sidossis
mesh_terms: D000328:Adult; D001481:Basal Metabolism; D001706:Biopsy; D002056:Burns / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D019069:Cell Respiration; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012146:Rest; D012720:Severity of Illness Index; D055815:Young Adult
keywords: burn injury; mitochondria; skeletal muscle