Progressive resistance training prevents loss of muscle mass and strength in bile duct‐ligated rats

Abstract

Background Loss of muscle mass and strength is common in cirrhosis and increases the risk of hyperammonaemia and hepatic encephalopathy. Resistance training optimizes muscle mass and strength in several chronic diseases. However, the beneficial effects of resistance training in cirrhosis remain to be investigated. Bile duct‐ligated (BDL) rats develop chronic liver disease, hyperammonaemia, reduced muscle mass and strength. Our aim was to test the effects of resistance training on muscle mass, function and ammonia metabolism in BDL‐rats. Methods A group of BDL‐rats underwent a progressive resistance training programme and a group of non‐exercise BDL‐rats served as controls. Resistance training comprised of ladder climbing with a progressive increase in carrying weights attached to the tail. Training was performed 5 days a week during 4 weeks. Muscle strength and body composition were assessed using grip strength and EchoMRI. Weight and circumference of the gastrocnemius muscle (normalized to bodyweight), plasma ammonia and glutamine synthetase protein expression and activity were assessed. Results BDL + exercise rats had significantly larger gastrocnemius circumference compared to non‐exercise BDL‐rats: ratio 0.082 vs 0.075 (P < 0.05). Gastrocnemius muscle weight was higher in exercisers than controls: 0.006 vs 0.005 (P < 0.05). A tendency towards a lower plasma ammonia in the exercise group compared to controls was observed (P = 0.10). There were no differences in lean body mass, GS protein expression and activity between the groups. Conclusion Resistance training in rats with chronic liver disease beneficially effects muscle mass and strength. The effects were followed by non‐significant reduction in blood ammonia; however, a tendency was observed.

Growing muscle against cirrhosis: In the quest for models to revealing mechanisms

“…The removal of ammonia by the muscle stems from its constitutive expression of glutamine synthetase, which mediates the formation of the “non‐toxic ammonia‐carrier” glutamine from glutamate and ammonia. Of note, the post‐translational increase in the activity of glutamine synthetase in skeletal muscle described in hyperammonaemic conditions was not affected by resistance training in the present study . On the other hand, the pathogenesis of sarcopaenia in cirrhosis is known to be multifactorial (malnutrition, inflammation, sedentarism, hypercatabolism), but ammonia is thought to be a primary mediator.…”

“…The supporting evidence, however, is still limited, and numerous clinical and pathophysiological questions have not been fully elucidated. In this regard, the experimental model reported by Aamann et al in this issue of Liver International represents a major step forward.…”

“…In their study, Aamann et al demonstrate the feasibility of performing a progressive resistance training protocol in rats with cirrhosis induced by bile‐duct ligation (BDL). The BDL model is known to reproduce in rodents the loss of muscle mass, malnutrition and other characteristic extrahepatic complications of cirrhosis such as hepatic encephalopathy .…”

“…Schematic of the progressive resistance training protocol developed in rats with bile‐duct ligation by Aamann et al and the major findings of their study. In the muscle, the enzyme glutamine synthetase forms glutamine from glutamate and ammonia, becoming a major route of ammonia detoxification in hyperammonaemic conditions.…”

“…Considerable evidences exist that hyperammonaemia causes important derangements in skeletal muscle, including mitochondrial dysfunction, oxidative stress and increased expression of myostatin, autophagy and cataplerosis ultimately resulting in severe metabolic and energy disturbances . Whether this vicious cycle between hyperammonaemia and muscle loss can be interrupted by physical activity is still unclear, but the observation by Aamann et al that resistance training improved muscle mass in BDL rats despite the presence of hyperammonaemia is encouraging.…”