RESUMO
AIMS: We aimed to investigate the impact of cancer cachexia and previous aerobic exercise training (AET) on cardiac function and structure in tumor bearing mice. MAIN METHODS: Colon adenocarcinoma cells 26 (CT26) were subcutaneously injected in BALB/c mice to establish robust cancer cachexia model. AET was performed on a treadmill during 45 days, 60 min/5 days per week. Cardiac function was evaluated by echocardiography and cardiac morphology was assessed by light microscopy. The protein expression levels of mitochondrial complex were analyzed by Western blotting. The mRNA levels of genes related to cardiac remodeling and autophagy were analyzed by quantitative Real-Time PCR. KEY FINDINGS: Our data confirms CT26 tumor bearing mice as a well-characterized and robust model of cancer cachexia. CT26 mice exhibited cardiac remodeling and dysfunction characterized by cardiac atrophy and impaired left ventricle ejection fraction paralleled by cardiac necrosis, inflammation and fibrosis. AET partially reversed the left ventricle ejection fraction and led to significant anti-cardiac remodeling effect associated reduced necrosis, inflammation and cardiac collagen deposition in CT26 mice. Reduced TGF-ß1 mRNA levels, increased mitochondrial complex IV protein levels and partial recovery of BNIP3 mRNA levels in cardiac tissue were associated with the cardiac effects of AET in CT26 mice. Thus, we suggest AET as a powerful regulator of key pathways involved in cardiac tissue homeostasis in cancer cachexia. SIGNIFICANCE: Our study provides a robust model of cancer cachexia, as well as highlights the potential and integrative effects of AET as a preventive strategy for reducing cardiac damage in cancer cachexia.
Assuntos
Caquexia/etiologia , Neoplasias do Colo/complicações , Cardiopatias/terapia , Condicionamento Físico Animal , Remodelação Ventricular , Animais , Caquexia/patologia , Neoplasias do Colo/patologia , Cardiopatias/etiologia , Cardiopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
ß(2)-adrenergic receptor (ß(2)-AR) agonists have been used as ergogenics by athletes involved in training for strength and power in order to increase the muscle mass. Even though anabolic effects of ß(2)-AR activation are highly recognized, less is known about the impact of ß(2)-AR in endurance capacity. We presently used mice lacking ß(2)-AR [ß(2)-knockout (ß(2) KO)] to investigate the role of ß(2)-AR on exercise capacity and skeletal muscle metabolism and phenotype. ß(2) KO mice and their wild-type controls (WT) were studied. Exercise tolerance, skeletal muscle fiber typing, capillary-to-fiber ratio, citrate synthase activity and glycogen content were evaluated. When compared with WT, ß(2) KO mice displayed increased exercise capacity (61%) associated with higher percentage of oxidative fibers (21% and 129% of increase in soleus and plantaris muscles, respectively) and capillarity (31% and 20% of increase in soleus and plantaris muscles, respectively). In addition, ß(2) KO mice presented increased skeletal muscle citrate synthase activity (10%) and succinate dehydrogenase staining. Likewise, glycogen content (53%) and periodic acid-Schiff staining (glycogen staining) were also increased in ß(2) KO skeletal muscle. Altogether, these data provide evidence that disruption of ß(2)-AR improves oxidative metabolism in skeletal muscle of ß(2) KO mice and this is associated with increased exercise capacity.