Prior Alcohol Use does not Enhance Skeletal Muscle Atrophy and Force Decrements Induced by Cancer Cachexia

Abstract

Introduction/objectiveAlcohol (EtOH) is a well‐known myotoxin with up to 60% of alcoholics suffering from alcoholic myopathy, characterized by progressive weakening and atrophy of proximal muscles. EtOH consumption is also associated with increased risk of cancer and continued EtOH intake enhances a primary comorbidity of cancer, cancer cachexia, or the loss of skeletal muscle strength and mass. However, the effects of prior EtOH use on cancer cachexia remains unknown. Therefore, the study objective was to determine if the cessation of EtOH prior to cancer development influences skeletal muscle force production, fatigability, and twitch characteristics.HypothesisWe hypothesize that discontinuing EtOH use prior to cancer progression will have no effect on skeletal muscle force production in tumor bearing mice.MethodsMale CD2F1 mice acclimated to a non‐EtOH containing Lieber DeCarli liquid diet for one week. Then, the concentration of EtOH was increased to 20% EtOH kcal/day for 6 weeks in EtOH mice. Mice then returned to non‐EtOH containing diet and C26 colon cancer cells were inoculated into the right flank of cancer groups. After 2‐3 weeks of cancer development muscle function was assessed. Mice were anesthetized, with the distal tendon of the lower leg attached to a servomotor, stimulating the posterior crural muscle complex by percutaneous electrodes. Peak isometric force was taken at 100 Hz, while fatigability was assessed using 60 isometric contractions produced over 4‐mins given at 100 Hz, and fatigue recovery measured using 100 Hz stimulations at 5‐ and 10‐minutes later. Triceps surae complex was excised and weighed following the force protocol.ResultsCancer reduced triceps surae muscle weight in both control and EtOH consuming mice (p < 0.0001). Cancer reduced force production (p= 0.009) of 100 Hz tetanic stimulation while no further effect of EtOH was observed. Main effects of C26 (p< 0.0001) were observed for fatigue within both diets, revealing reduced force production and increased fatigue. Force production was decreased across the fatigue protocol in all groups (p< 0.0001), while main effects of C26 (p<0.0001) were observed within the control and EtOH diets, revealing similarly reduced force production and increased fatigue regardless of EtOH status. Fatigue recovery was also similar across all groups. Twitch half relaxation was increased in C26 mice (p= 0.0283), showing a disruption in relaxation that is cancer dependent and not exacerbated by EtOH. No changes in twitch maximum force or rate of force development were noted between groups.ConclusionsTumor‐bearing mice produced less force during a tetanic stimulation and fatigue protocol, in accordance with significant muscle atrophy of the triceps surae. The prior consumption of EtOH did not worsen cancer‐induced deficits in skeletal muscle contraction. As it has been shown previously that the continuation of EtOH throughout the progression of cancer enhances cancer cachexia, these data exemplify the clinical benefits of stopping EtOH consumption as early as possible.