The high-intensity interval training mitigates the cardiac remodeling in spontaneously hypertensive rats.

AIM: To evaluate the influence of high-intensity interval training (HIIT) on cardiac structural and functional characteristics and myocardial mitogen-activated protein kinase (MAPK) signaling in hypertensive rats. METHODS: Male rats (12 months old) were divided into three groups: Wistar Kyoto rats (WKY, n = 8); sedentary spontaneously hypertensive rats (SED-SHR, n = 10), and trained spontaneously hypertensive rats (HIIT-SHR, n = 10). Systolic blood pressure (SBP), functional capacity, echocardiography, isolated papillary muscle, and gene expression of MAPK gene-encoding proteins associated with Elk1, cJun, ATF2, MEF2 were analyzed. KEY FINDINGS: HIIT decreased SBP and increased functional capacity, left ventricular diastolic diameter, posterior wall thickness-left ventricle, relative wall thickness-left ventricle, and resting tension of the papillary muscle. In hypertensive rats, we observed a decrease in the gene-encoding ATF2 protein; this decrease was reversed by HIIT. SIGNIFICANCE: The influence of HIIT in the SHR model in the compensated hypertension phase generated an increase in cardiac hypertrophy, attenuated myocardial diastolic dysfunction, lowered blood pressure, improved functional capacity, and reversed the alteration in gene-encoding ATF2 protein.

MicroRNA-mRNA Co-sequencing Identifies Transcriptional and Post-transcriptional Regulatory Networks Underlying Muscle Wasting in Cancer Cachexia.

Cancer cachexia is a metabolic syndrome with alterations in gene regulatory networks that consequently lead to skeletal muscle wasting. Integrating microRNAs-mRNAs omics profiles offers an opportunity to understand transcriptional and post-transcriptional regulatory networks underlying muscle wasting. Here, we used RNA sequencing to simultaneously integrate and explore microRNAs and mRNAs expression profiles in the tibialis anterior (TA) muscles of the Lewis Lung Carcinoma (LLC) model of cancer cachexia. We found 1,008 mRNAs and 18 microRNAs differentially expressed in cachectic mice compared with controls. Although our transcriptomic analysis demonstrated a high heterogeneity in mRNA profiles of cachectic mice, we identified a reduced number of differentially expressed genes that were uniformly regulated within cachectic muscles. This set of uniformly regulated genes is associated with the extracellular matrix (ECM), proteolysis, and inflammatory response. We also used transcriptomic data to perform enrichment analysis of transcriptional factor binding sites in promoter sequences, which revealed activation of the atrophy-related transcription factors NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and microRNA expression profiles identified post-transcriptional regulation by microRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and the FoxO signaling pathway. Our integrative analysis of microRNA-mRNA co-profiles comprehensively characterized regulatory relationships of molecular pathways and revealed microRNAs targeting ECM-associated genes in cancer cachexia.

Creatine does not promote hypertrophy in skeletal muscle in supplemented compared with nonsupplemented rats subjected to a similar workload.

The purpose of this study was to test the hypothesis that creatine (Cr) supplementation may promote an additional hypertrophic effect on skeletal muscle independent of a higher workload on Cr-supplemented trained muscle compared with Cr-nonsupplemented trained muscle. Male Wistar rats (2-3 months old, 250-300 g) were divided randomly into 4 groups (n = 8 per group): nontrained without Cr supplementation (CO), nontrained with Cr supplementation (CR), trained without Cr supplementation (TR), and trained with Cr supplementation (TRCR). Creatine supplementation was given at 0.5 g/kg per day. Trained groups were submitted to a 5-week resistance training program (5 d/wk). The progressive workloads were similar between the Cr-supplemented (TRCR) and Cr-nonsupplemented (TR) trained groups; the only difference between groups was the Cr treatment. After the 5-week experiment, the soleus muscle was dissected to analyze the cross-sectional area (CSA) of the muscle fibers. Resistance training promoted a significant (P < .05) increase in the muscle fibers CSA in the TR group compared with the CO group. However, no additional hypertrophic effect was found when Cr supplementation was added to training (TRCR vs TR comparison, P > .05). In addition, Cr supplementation alone did not promote significant alterations in muscle fiber CSA (CR vs CO comparison, P > .05). We conclude that Cr supplementation does not promote any additional hypertrophic effect on skeletal muscle area when Cr-supplemented trained muscles are submitted to same training regimen than Cr-nonsupplemented trained muscles. Specifically, any benefits of Cr supplementation on hypertrophy gains during resistance training may not be attributed to a direct anabolic effect on the skeletal muscle.