Blunted cardiomyocyte remodeling response in exercise-resistant rats

Increasing a subject’s aerobic exercise capacity with training decreases cardiovascular morbidity and mortality. Of major concern is the key observation that up to 20% of subjects demonstrate little or no change in maximal oxygen consumption (VO2max) with exercise training (1) and can be considered exercise resistant. Our goal with the current research was to test the hypothesis that variation in training response is associated with cardiomyocyte functional response to training

Aerobic interval training reduces cardiovascular risk factors more than a multitreatment approach in overweight adolescents

A B S T R A C T The aim of the present study was to compare the effects of a multidisciplinary approach (MTG) and aerobic interval training (AIT) on cardiovascular risk factors in overweight adolescents. A total of 62 overweight and obese adolescents from Trøndelag County in Norway, referred to medical treatment at St Olav's Hospital, Trondheim, Norway, were invited to participate. Of these, 54 adolescents (age, 14.0 + − 0.3 years) were randomized to either AIT (4 × 4 min intervals at 90 % of maximal heart rate, each interval separated by 3 min at 70 %, twice a week for 3 months) or to MTG (exercise, dietary and psychological advice, twice a month for 12 months). Follow-up testing occurred at 3 and 12 months.VO 2 max (maximal oxygen uptake) increased more after AIT compared with MTG, both at 3 months (11 compared with 0 %; P < 0.01) and 12 months (12 compared with −1 %; P < 0.01). AIT enhanced endothelial function compared with MTG at both 3 months (absolute change, 5.1 compared with 3.9 %; P < 0.01) and 12 months (absolute change, 6.3 compared with 1.0 %; P < 0.01). AIT was favourable compared with MTG in reducing BMI (body mass index), percentage of fat, MAP (mean arterial blood pressure) and increasing peak oxygen pulse. In addition, AIT induced a more favourable regulation of blood glucose and insulin compared with MTG. In conclusion, the novel findings of the present proof-of-concept study was that 3 months of twice weekly high-intensity exercise sessions reduced several known cardiovascular risk factors in obese adolescents more than that observed after a multitreatment strategy, which was initiated as hospital treatment. Follow-up at 12 months confirmed that AIT improved or maintained these risk factors to a better degree than MTG

COX7A2L genetic variants determine cardiorespiratory fitness in mice and human

Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness.Mitochondrial respiratory complexes form superassembled structures called supercomplexes. COX7A2L is a supercomplex-specific assembly factor in mammals, although its implication for supercomplex formation and cellular metabolism remains controversial. Here we identify a role for COX7A2L for mitochondrial supercomplex formation in humans. By using human cis-expression quantitative trait loci data, we highlight genetic variants in the COX7A2L gene that affect its skeletal muscle expression specifically. The most significant cis-expression quantitative trait locus is a 10-bp insertion in the COX7A2L 3 ' untranslated region that increases messenger RNA stability and expression. Human myotubes harboring this insertion have more supercomplexes and increased respiration. Notably, increased COX7A2L expression in the muscle is associated with lower body fat and improved cardiorespiratory fitness in humans. Accordingly, specific reconstitution of Cox7a2l expression in C57BL/6J mice leads to higher maximal oxygen consumption, increased lean mass and increased energy expenditure. Furthermore, Cox7a2l expression in mice is induced specifically in the muscle upon exercise. These findings elucidate the genetic basis of mitochondrial supercomplex formation and function in humans and show that COX7A2L plays an important role in cardiorespiratory fitness, which could have broad therapeutic implications in reducing cardiovascular mortality.Peer reviewe

COX7A2L genetic variants determine cardiorespiratory fitness in mice and human

Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness.Mitochondrial respiratory complexes form superassembled structures called supercomplexes. COX7A2L is a supercomplex-specific assembly factor in mammals, although its implication for supercomplex formation and cellular metabolism remains controversial. Here we identify a role for COX7A2L for mitochondrial supercomplex formation in humans. By using human cis-expression quantitative trait loci data, we highlight genetic variants in the COX7A2L gene that affect its skeletal muscle expression specifically. The most significant cis-expression quantitative trait locus is a 10-bp insertion in the COX7A2L 3 ' untranslated region that increases messenger RNA stability and expression. Human myotubes harboring this insertion have more supercomplexes and increased respiration. Notably, increased COX7A2L expression in the muscle is associated with lower body fat and improved cardiorespiratory fitness in humans. Accordingly, specific reconstitution of Cox7a2l expression in C57BL/6J mice leads to higher maximal oxygen consumption, increased lean mass and increased energy expenditure. Furthermore, Cox7a2l expression in mice is induced specifically in the muscle upon exercise. These findings elucidate the genetic basis of mitochondrial supercomplex formation and function in humans and show that COX7A2L plays an important role in cardiorespiratory fitness, which could have broad therapeutic implications in reducing cardiovascular mortality

A Multi-Center Comparison of VO2peak Trainability Between Interval Training and Moderate Intensity Continuous Training

There is heterogeneity in the observed VO2peak response to similar exercise training, and different exercise approaches produce variable degrees of exercise response (trainability). The aim of this study was to combine data from different laboratories to compare VO2peak trainability between various volumes of interval training and Moderate Intensity Continuous Training (MICT). For interval training, volumes were classified by the duration of total interval time. High-volume High Intensity Interval Training (HIIT) included studies that had participants complete more than 15 min of high intensity efforts per session. Low-volume HIIT/Sprint Interval Training (SIT) included studies using less than 15 min of high intensity efforts per session. In total, 677 participants across 18 aerobic exercise training interventions from eight different universities in five countries were included in the analysis. Participants had completed 3 weeks or more of either high-volume HIIT (n = 299), low-volume HIIT/SIT (n = 116), or MICT (n = 262) and were predominately men (n = 495) with a mix of healthy, elderly and clinical populations. Each training intervention improved mean VO2peak at the group level (P \u3c 0.001). After adjusting for covariates, high-volume HIIT had a significantly greater (P \u3c 0.05) absolute VO2peak increase (0.29 L/min) compared to MICT (0.20 L/min) and low-volume HIIT/SIT (0.18 L/min). Adjusted relative VO2peak increase was also significantly greater (P \u3c 0.01) in high-volume HIIT (3.3 ml/kg/min) than MICT (2.4 ml/kg/min) and insignificantly greater (P = 0.09) than low-volume HIIT/SIT (2.5 mL/kg/min). Based on a high threshold for a likely response (technical error of measurement plus the minimal clinically important difference), high-volume HIIT had significantly more (P \u3c 0.01) likely responders (31%) compared to low-volume HIIT/SIT (16%) and MICT (21%). Covariates such as age, sex, the individual study, population group, sessions per week, study duration and the average between pre and post VO2peak explained only 17.3% of the variance in VO2peak trainability. In conclusion, high-volume HIIT had more likely responders to improvements in VO2peak compared to low-volume HIIT/SIT and MICT

Circulating MicroRNAs and Aerobic Fitness - The HUNT-Study

© 2013 Bye et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Powerful extreme phenotype sampling designs and score tests for genetic association studies

We consider cross‐sectional genetic association studies (common and rare variants) where non‐genetic information is available or feasible to obtain for N individuals, but where it is infeasible to genotype all N individuals. We consider continuously measurable Gaussian traits (phenotypes). Genotyping n < N extreme phenotype individuals can yield better power to detect phenotype‐genotype associations, as compared to randomly selecting n individuals. We define a person as having an extreme phenotype if the observed phenotype is above a specified threshold or below a specified threshold. We consider a model where these thresholds can be tailored to each individual. The classical extreme sampling design is to set equal thresholds for all individuals. We introduce a design (z‐extreme sampling) where personalized thresholds are defined based on the residuals of a regression model including only non‐genetic (fully available) information. We derive score tests for the situation where only n extremes are analyzed (complete case analysis) and for the situation where the non‐genetic information on N − n non‐extremes is included in the analysis (all case analysis). For the classical design, all case analysis is generally more powerful than complete case analysis. For the z‐extreme sample, we show that all case and complete case tests are equally powerful. Simulations and data analysis also show that z‐extreme sampling is at least as powerful as the classical extreme sampling design and the classical design is shown to be at times less powerful than random sampling. The method of dichotomizing extreme phenotypes is also discussed

MicroRNAs as important regulators of exercise adaptation

A significant body of evidence supports the protective role of exercise training (ET) in cardiovascular diseases, skeletal muscle dystrophies, several types of cancer, Alzheimer disease or even in the recovery of spinal cord injury. In spite of this, the molecular mechanisms underlying the beneficial effects of exercise training are not well understood and remain elusive. Several mechanisms have been proposed in the past, but more recently microRNAs (miRNAs), small non-coding RNA molecules involved in a variety of basic biological processes that negatively modulate gene expression, recognized as important regulatory molecules. In this review, we highlight recent advances on the miRNA involvement in the benefits of ET. Here, we assess the role of microRNAs expressed in the heart, in the skeletal muscle, detected in the circulation (serum and plasma), and in other conditions (e.g., spinal cord injury). Additionally, the long-term effects of diverse ET modalities (e.g., running, cycling, resistance training) in the cardiac miRNA profile are properly addressed

A small molecule activator of AKT does not reduce ischemic injury of the rat heart

Background Activation of protein kinase AKT is required for cardioprotection by ischemic preconditioning, and transgenic overexpression of AKT protects the heart against ischemia. However, it is unknown whether acute pharmacological activation of AKT alone, using a therapeutically relevant strategy, induces cardioprotection. In this study we provide the first evidence to clarify this question. Methods We used a recently described specific activator of AKT, the small molecule SC79, to treat rat hearts submitted to ischemia and reperfusion. Initially, isolated rat hearts were perfused with increasing doses of SC79 to verify the magnitude of AKT activation. Low and high doses were determined and used to treat hearts submitted to ischemia (35 minutes) and reperfusion (60 minutes), in a randomized and blinded design. AKT activation was verified by western immunobloting. Metabolic profile was determined by cardiac ATP content and mitochondrial enzyme activity, while cytosolic levels of cytochrome C and caspase-3 activity were used as markers of apoptosis. Ischemic injury was assessed by quantification of infarct size and cardiac release of creatine kinase and lactate dehydrogenase. Results SC79 activated cardiac AKT within 30 minutes in a dose-dependent fashion. ATP content was largely reduced by ischemia, but was not rescued by SC79. Similarly, mitochondrial enzyme activity was not affected by SC79. SC79 administered before ischemia or at reperfusion did not prevent cytosolic accumulation of cytochrome C and overactivation of caspase-3. Finally, SC79 failed to reduce infarct size or release of cardiac injury biomarkers at reperfusion. Conclusion We conclude that selective AKT activation by the synthetic molecule SC79 does not protect the rat heart against ischemic injury, indicating that acute pharmacological activation of AKT is not sufficient for cardioprotection