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.
authors.affiliation: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th. Street BLSB 306, Philadelphia, PA, 19107, USA.
authors.forename: Felipe E
authors.initials: FE
authors.lastname: Pedroso
authors.forename: Paul B
authors.initials: PB
authors.lastname: Spalding
authors.forename: Michael C
authors.initials: MC
authors.lastname: Cheung
authors.forename: Relin
authors.initials: R
authors.lastname: Yang
authors.forename: Juan C
authors.initials: JC
authors.lastname: Gutierrez
authors.forename: Andrea
authors.initials: A
authors.lastname: Bonetto
authors.forename: Rui
authors.initials: R
authors.lastname: Zhan
authors.forename: Ho Lam
authors.initials: HL
authors.lastname: Chan
authors.forename: Nicholas
authors.initials: N
authors.lastname: Namias
authors.forename: Leonidas G
authors.initials: LG
authors.lastname: Koniaris
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Zimmers