Journal of Cachexia, Sarcopenia and Muscle (JCSM) - Abstract


Volume 3, Number 3, Page 199 - 211

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 G. Koniaris and Teresa A. Zimmers

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.

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 G., Zimmers Teresa A., Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia J Cachex Sarcopenia Muscle 2012;3:199-211