Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia

Felipe E. Pedroso, Paul B. Spalding, Michael C. Cheung, Relin Yang, Juan C. Gutierrez, Andrea Bonetto, Rui Zhan, Ho Lam Chan, Nicholas Namias, Leonidas Koniaris, Teresa Zimmers

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking. Methods: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay. Results: Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects. Conclusions: This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia.

Original languageEnglish (US)
Pages (from-to)199-211
Number of pages13
JournalJournal of Cachexia, Sarcopenia and Muscle
Volume3
Issue number3
DOIs
StatePublished - Sep 2012
Externally publishedYes

Fingerprint

Hyperphagia
Cachexia
Inflammation
Muscles
Wounds and Injuries
Burns
Bone Density
Fats
Body Weight
Polydipsia
Organ Size
Acute-Phase Proteins
Ligases
Ubiquitin
Body Composition
Inbred C57BL Mouse
Chemokines
Wound Healing
Drinking
Survivors

Keywords

  • Animal model
  • Metabolism
  • Muscle atrophy
  • Muscle wasting
  • Thermal injury

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physiology (medical)

Cite this

Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia. / Pedroso, Felipe E.; Spalding, Paul B.; Cheung, Michael C.; Yang, Relin; Gutierrez, Juan C.; Bonetto, Andrea; Zhan, Rui; Chan, Ho Lam; Namias, Nicholas; Koniaris, Leonidas; Zimmers, Teresa.

In: Journal of Cachexia, Sarcopenia and Muscle, Vol. 3, No. 3, 09.2012, p. 199-211.

Research output: Contribution to journalArticle

Pedroso, FE, Spalding, PB, Cheung, MC, Yang, R, Gutierrez, JC, Bonetto, A, Zhan, R, Chan, HL, Namias, N, Koniaris, L & Zimmers, T 2012, 'Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia', Journal of Cachexia, Sarcopenia and Muscle, vol. 3, no. 3, pp. 199-211. https://doi.org/10.1007/s13539-012-0062-x
Pedroso, Felipe E. ; Spalding, Paul B. ; Cheung, Michael C. ; Yang, Relin ; Gutierrez, Juan C. ; Bonetto, Andrea ; Zhan, Rui ; Chan, Ho Lam ; Namias, Nicholas ; Koniaris, Leonidas ; Zimmers, Teresa. / Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia. In: Journal of Cachexia, Sarcopenia and Muscle. 2012 ; Vol. 3, No. 3. pp. 199-211.
@article{7a5b3ce931454ea79bb398f96ff7a798,
title = "Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia",
abstract = "Background: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking. Methods: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay. Results: Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects. Conclusions: This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia.",
keywords = "Animal model, Metabolism, Muscle atrophy, Muscle wasting, Thermal injury",
author = "Pedroso, {Felipe E.} and Spalding, {Paul B.} and Cheung, {Michael C.} and Relin Yang and Gutierrez, {Juan C.} and Andrea Bonetto and Rui Zhan and Chan, {Ho Lam} and Nicholas Namias and Leonidas Koniaris and Teresa Zimmers",
year = "2012",
month = "9",
doi = "10.1007/s13539-012-0062-x",
language = "English (US)",
volume = "3",
pages = "199--211",
journal = "Journal of Cachexia, Sarcopenia and Muscle",
issn = "2190-5991",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia

AU - Pedroso, Felipe E.

AU - Spalding, Paul B.

AU - Cheung, Michael C.

AU - Yang, Relin

AU - Gutierrez, Juan C.

AU - Bonetto, Andrea

AU - Zhan, Rui

AU - Chan, Ho Lam

AU - Namias, Nicholas

AU - Koniaris, Leonidas

AU - Zimmers, Teresa

PY - 2012/9

Y1 - 2012/9

N2 - Background: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking. Methods: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay. Results: Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects. Conclusions: This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia.

AB - Background: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking. Methods: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay. Results: Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects. Conclusions: This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia.

KW - Animal model

KW - Metabolism

KW - Muscle atrophy

KW - Muscle wasting

KW - Thermal injury

UR - http://www.scopus.com/inward/record.url?scp=84865736276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865736276&partnerID=8YFLogxK

U2 - 10.1007/s13539-012-0062-x

DO - 10.1007/s13539-012-0062-x

M3 - Article

C2 - 22476919

AN - SCOPUS:84865736276

VL - 3

SP - 199

EP - 211

JO - Journal of Cachexia, Sarcopenia and Muscle

JF - Journal of Cachexia, Sarcopenia and Muscle

SN - 2190-5991

IS - 3

ER -