Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.

Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression.

Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26). Exercise training also slowed tumor growth in melanoma B16F10, colon tumor 26 (CT26), and Lewis lung carcinoma (LLC) tumor-bearing mice, with minor effects in mammary carcinoma 4T1, MDA-MB-231, and MMTV-PyMT mice. In silico analyses using transcriptome profiles derived from these models revealed that platelet factor 4 (Pf4) is one of the main upregulated genes associated with splenomegaly during cancer progression. To understand whether exercise training would modulate the expression of these genes in the tumor and spleen, we investigated particularly the CT26 model, which displayed splenomegaly and had a clear response to the exercise training effects. RT-qPCR analysis confirmed that trained CT26 tumor-bearing mice had decreased Pf4 mRNA levels in both the tumor and spleen when compared to untrained CT26 tumor-bearing mice. Furthermore, exercise training specifically decreased Pf4 mRNA levels in the CT26 tumor cells. Aspirin treatment did not change tumor growth, splenomegaly, and tumor Pf4 mRNA levels, confirming that exercise decreased non-platelet Pf4 mRNA levels. Finally, tumor Pf4 mRNA levels are deregulated in The Cancer Genome Atlas Program (TCGA) samples and predict survival in multiple cancer types. This highlights the potential therapeutic value of exercise as a complementary approach to cancer treatment and underscores the importance of understanding the exercise-induced transcriptional changes in the spleen for the development of novel cancer therapies.

Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice.

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers' cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.

Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation.

Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia.

Aerobic exercise training and in vivo Akt activation counteract cancer cachexia by inducing a hypertrophic Profile through eIF-2α modulation / Treinamento de exercício aeróbico e ativação de Akt in vivo neutralizam a caquexia do câncer induzindo um perfil hipertrófico através da modulação eIF-2α

Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia.

Additive effects of beta-alanine and sodium bicarbonate on upper-body intermittent performance.

We examined the isolated and combined effects of beta-alanine (BA) and sodium bicarbonate (SB) on high-intensity intermittent upper-body performance in judo and jiu-jitsu competitors. 37 athletes were assigned to one of four groups: (1) placebo (PL)+PL; (2) BA+PL; (3) PL+SB or (4) BA+SB. BA or dextrose (placebo) (6.4 g day⁻¹) was ingested for 4 weeks and 500 mg kg⁻¹ BM of SB or calcium carbonate (placebo) was ingested for 7 days during the 4th week. Before and after 4 weeks of supplementation, the athletes completed four 30-s upper-body Wingate tests, separated by 3 min. Blood lactate was determined at rest, immediately after and 5 min after the 4th exercise bout, with perceived exertion reported immediately after the 4th bout. BA and SB alone increased the total work done in +7 and 8 %, respectively. The co-ingestion resulted in an additive effect (+14 %, p < 0.05 vs. BA and SB alone). BA alone significantly improved mean power in the 2nd and 3rd bouts and tended to improve the 4th bout. SB alone significantly improved mean power in the 4th bout and tended to improve in the 2nd and 3rd bouts. BA+SB enhanced mean power in all four bouts. PL+PL did not elicit any alteration on mean and peak power. Post-exercise blood lactate increased with all treatments except with PL+PL. Only BA+SB resulted in lower ratings of perceived exertion (p = 0.05). Chronic BA and SB supplementation alone equally enhanced high-intensity intermittent upper-body performance in well-trained athletes. Combined BA and SB promoted a clear additive ergogenic effect.

Anthropometric, physiological, performance, and nutritional profile of the Brazil National Canoe Polo Team.

The purpose of this study was to determine the physiological, anthropometric, performance, and nutritional characteristics of the Brazil Canoe Polo National Team. Ten male canoe polo athletes (age 26.7 ± 4.1 years) performed a battery of tests including assessments of anthropometric parameters, upper-body anaerobic power (Wingate), muscular strength, aerobic power, and nutritional profile. In addition, we characterized heart rate and plasma lactate responses and the temporal pattern of the effort/recovery during a simulated canoe polo match. The main results are as follows: body fat, 12.3 ± 4.0%; upper-body peak and mean power, 6.8 ± 0.5 and 4.7 ± 0.4 W · kg(-1), respectively; 1-RM bench press, 99.1 ± 11.7 kg; peak oxygen uptake, 44.3 ± 5.8 mL · kg(-1) · min(-1); total energy intake, 42.8 ± 8.6 kcal · kg(-1); protein, carbohydrate, and fat intakes, 1.9 ± 0.1, 5.0 ± 1.5, and 1.7 ± 0.4 g · kg(-1), respectively; mean heart rate, 146 ± 11 beats · min(-1); plasma lactate, 5.7 ± 3.8 mmol · L(-1) at half-time and 4.6 ± 2.2 mmol · L(-1) at the end of the match; effort time (relative to total match time), 93.1 ± 3.0%; number of sprints, 9.6 ± 4.4. The results of this study will assist coaches, trainers, and nutritionists in developing more adequate training programmes and dietary interventions for canoe polo athletes.