Aerobic Exercise Training Prevents Heart Failure-Induced Skeletal Muscle Atrophy by Anti-Catabolic, but Not Anabolic Actions

Abstract

BackgroundHeart failure (HF) is associated with cachexia and consequent exercise intolerance. Given the beneficial effects of aerobic exercise training (ET) in HF, the aim of this study was to determine if the ET performed during the transition from cardiac dysfunction to HF would alter the expression of anabolic and catabolic factors, thus preventing skeletal muscle wasting.Methods and ResultsWe employed ascending aortic stenosis (AS) inducing HF in Wistar male rats. Controls were sham-operated animals. At 18 weeks after surgery, rats with cardiac dysfunction were randomized to 10 weeks of aerobic ET (AS-ET) or to an untrained group (AS-UN). At 28 weeks, the AS-UN group presented HF signs in conjunction with high TNF-α serum levels; soleus and plantaris muscle atrophy; and an increase in the expression of TNF-α, NFκB (p65), MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented, as well as muscle wasting, and the atrophy promoters were decreased. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR) were not observed. Nevertheless, in the plantaris muscle, ET maintained high PGC1α levels.ConclusionsThus, the ET capability to attenuate cardiac function during the transition from cardiac dysfunction to HF was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors, but through anti-catabolic activity, presumably caused by PGC1α action. These findings indicate the therapeutic potential of aerobic ET to block HF-induced muscle atrophy by counteracting the increased catabolic state.

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

“…In many cardiovascular diseases including CHF, exercise training has been recognized as an evidence‐based therapeutic strategy with prognostic benefits improving risk factor such as hyperlipidemia, hypertension and coronary endothelial function . It has been shown that exercise training not only has cardio‐protective effects and slows down the transition from cardiac dysfunction to (chronic) heart failure but also induces anti‐catabolic signaling in skeletal muscle, possibly by induction of PGC1α . The beneficial effect of resistance exercise training was also observed on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy .…”

Skeletal muscle wasting in chronic heart failure

“…46,83-85 Supplementation of a low-dose creatine in combination with resistance training improved lean mass in elderly over a period of 12 weeks. 92 In breast cancer patients undergoing adjuvant chemotherapy, a favourable effect of resistance exercise training was seen on sarcopenia and dynapenia. 87 An accelerometer-determined physical activity showed an independent, dose-response relationship with lean mass percentage and lower limb strength.…”

Exercise during transition from compensated left ventricular hypertrophy to heart failure in aortic stenosis rats

“…LV hypertrophy can be observed 1 month after stenosis induction . Rats then remain compensated for 20‐28 weeks when they start to present heart failure features and evolve to death in 2‐4 weeks . In this study, the exercise protocol was initiated 18 weeks after AS surgery; at this time, no rat had tachypnoea/laboured respiration.…”

“…However, in the face of increased afterload and during the transition from compensated hypertrophy to heart failure, the further overload caused by exercise resulted in impaired MAPK pathway signalling, additional myocyte hypertrophy and a trend towards worse systolic function compared to sedentary AS rats. It is probable that the previously observed beneficial effects of exercise in chronic and persistent pressure overload occurred early in the remodelling process and not during the transition to clinical heart failure, when rats present advanced degrees of LV hypertrophy and dysfunction, thus preventing a reverse remodelling process.…”