Treadmill Exercise And IL-6-induced Cachexia In The ApcMin/+ Mouse

Abstract

Cancer cachexia is a condition associated with the loss of skeletal muscle and adipose tissue mass. The ApcMin/+ mouse is an established model of colorectal cancer that also develops cachexia. IL-6 is necessary for the development of cachexia in the ApcMin/+ mouse. While endurance exercise can reduce polyp number and systemic inflammation in the ApcMin/+ mouse, the affect of exercise on IL-6-induced cachexia in the ApcMin/+ mouse is not known. PURPOSE: The purpose of this study was to determine if 8 weeks of treadmill exercise could repress IL-6-induced cachexia in the ApcMin/+ mouse. METHODS: ApcMin/+ mice were assigned to either 8 weeks of treadmill (6 days/week, 18m/s, 5% grade) exercise or cage control treatments at 6 weeks of age. After 6 weeks of exercise training, circulating IL-6 over-expression was induced by electroporation of a plasmid into the quadriceps while an empty vector served as the control. Body weight, muscle and fat pad weights were recorded at 14 weeks of age. RESULTS: Electroporation increased circulating plasma IL-6 in sedentary control mice (6.7 vs 141 pg/ml) and the exercise group (10.4 vs 111 pg/ml). Sedentary ApcMin/+ mice over-expressing IL-6 lost 10.2% (p < 0.001) of their body mass during the 2 week period. The loss in body weight corresponded to a 13% reduction (p = 0.04) in soleus muscle wet weight and a 45% (p = 0.002) reduction in epididymal fat pad weight. Exercise training prevented the IL-6 induced loss in body weight and maintained soleus muscle and epididymal fat pad weights. CONCLUSION: These data show chronic moderate treadmill exercise in the ApcMin/+ mouse prevents cachexia induced by IL-6 over-expression. Funded by R01CA121249-01A2