Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

• Published in: Biochemical and biophysical research communications 2013-06, Vol.435 (3), p.488-492
• Main Authors: Roberts, B.M., Frye, G.S., Ahn, B., Ferreira, L.F., Judge, A.R.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; ATROPHY; C-26; Cachexia - etiology; Cachexia - pathology; Cachexia - physiopathology; CARCINOMAS; Cell Line, Tumor; Contractile dysfunction; DIAPHRAGM; Extremities; FATIGUE; LARGE INTESTINE; LIMBS; Male; MICE; Muscle atrophy; Muscle Fatigue - physiology; Muscle Fibers, Fast-Twitch - pathology; Muscle Fibers, Slow-Twitch - pathology; Muscle weakness; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Atrophy - etiology; Muscular Atrophy - pathology; Muscular Atrophy - physiopathology; MYOSIN; Neoplasms, Experimental - complications; Neoplasms, Experimental - physiopathology; OXIDATION
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.05.018

•C-26 cancer cachexia causes a significant decrease in limb muscle absolute force.•C-26 cancer cachexia causes a significant decrease in limb muscle specific force.•C-26 cancer cachexia decreases fatigue resistance in the soleus muscle.•C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle.•C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative soleus is also important for normal locomotion, we further performed a fatigue trial in the soleus and found that the decrease in relative force was greater and more rapid in solei from C-26 mice compared to controls. These data demonstrate that severe cancer cachexia causes profound muscle weakness that is not entirely explained by the muscle atrophy. In addition, cancer cachexia decreases the fatigue resistance of the soleus muscle, a postural muscle typically resistant to fatigue. Thus, specifically targeting contractile dysfunctio