Early-Onset Physical Inactivity and Metabolic Dysfunction in Tumor-bearing Mice Is Associated with Accelerated Cachexia.

Abstract

Male C57BL/6J mice (12 wk of age) were injected with 1 × 106 LLC cells or phosphate-buffered saline (PBS) subcutaneously in the right flank, and tissue was collected 26-28 d after cell injection. Tumor volume was measured every 5 d throughout the study to calculate the tumor growth rate. Fifteen days after tumor inoculation, a subset of PBS (n = 11) and LLC (n = 16) mice were individually housed in metabolic Comprehensive Laboratory Animal Monitoring System cages for 5 d. LLC mice exhibited greater body weight loss (-5.1%), decreased muscle mass (-7%), decreased fat mass (-22%), and increased plasma interleukin-6 (212%) compared with PBS mice. Before the onset of cachexia, total cage activity was decreased in tumor-bearing mice. Cage activity was negatively associated with tumor mass and positively associated with hindlimb muscle mass. In addition, LLC mice had greater lipid oxidation than PBS mice. LLC mice exhibit early-onset physical inactivity and altered systemic lipid oxidation, which are associated with the eventual development of cachexia.