Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely burned adults

Craig Porter, David Herndon, Elisabet Børsheim, Tony Chao, Paul T. Reidy, Michael S. Borack, Blake Rasmussen, Maria Chondronikola, Manish K. Saraf, Labros S. Sidossis

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)E462-E467
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume307
Issue number5
DOIs
StatePublished - Sep 1 2014

Fingerprint

Muscle Mitochondrion
Skeletal Muscle
Thermogenesis
Respiration
Oligomycins
Citrate (si)-Synthase
Indirect Calorimetry
Body Surface Area
Oxidative Phosphorylation
Quadriceps Muscle
Adrenergic Agents
Survivors
Biopsy
Temperature
Wounds and Injuries

Keywords

  • Burn injury
  • Mitochondria
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely burned adults. / Porter, Craig; Herndon, David; Børsheim, Elisabet; Chao, Tony; Reidy, Paul T.; Borack, Michael S.; Rasmussen, Blake; Chondronikola, Maria; Saraf, Manish K.; Sidossis, Labros S.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 307, No. 5, 01.09.2014, p. E462-E467.

Research output: Contribution to journalArticle

Porter, C, Herndon, D, Børsheim, E, Chao, T, Reidy, PT, Borack, MS, Rasmussen, B, Chondronikola, M, Saraf, MK & Sidossis, LS 2014, 'Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely burned adults', American Journal of Physiology - Endocrinology and Metabolism, vol. 307, no. 5, pp. E462-E467. https://doi.org/10.1152/ajpendo.00266.2014
Porter, Craig ; Herndon, David ; Børsheim, Elisabet ; Chao, Tony ; Reidy, Paul T. ; Borack, Michael S. ; Rasmussen, Blake ; Chondronikola, Maria ; Saraf, Manish K. ; Sidossis, Labros S. / Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely burned adults. In: American Journal of Physiology - Endocrinology and Metabolism. 2014 ; Vol. 307, No. 5. pp. E462-E467.
@article{5c2d1fab0b4743479216a7d386c3587a,
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.",
keywords = "Burn injury, Mitochondria, Skeletal muscle",
author = "Craig Porter and David Herndon and Elisabet B{\o}rsheim and Tony Chao and Reidy, {Paul T.} and Borack, {Michael S.} and Blake Rasmussen and Maria Chondronikola and Saraf, {Manish K.} and Sidossis, {Labros S.}",
year = "2014",
month = "9",
day = "1",
doi = "10.1152/ajpendo.00266.2014",
language = "English (US)",
volume = "307",
pages = "E462--E467",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely burned adults

AU - Porter, Craig

AU - Herndon, David

AU - Børsheim, Elisabet

AU - Chao, Tony

AU - Reidy, Paul T.

AU - Borack, Michael S.

AU - Rasmussen, Blake

AU - Chondronikola, Maria

AU - Saraf, Manish K.

AU - Sidossis, Labros S.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

AB - 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.

KW - Burn injury

KW - Mitochondria

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=84907741545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907741545&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00266.2014

DO - 10.1152/ajpendo.00266.2014

M3 - Article

VL - 307

SP - E462-E467

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 5

ER -