Tomas Venckunas

Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise

Significance High-intensity interval training (HIIT) has become popular because it is a time-efficient way to increase endurance. An intriguing and so-far-unanswered question is how a few minutes of HIIT can be that effective. We exposed recreationally active men to one session of three to six sets of 30-s high-intensity cycling exercise. Muscle biopsies taken 24 h later showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca2+ channels, the ryanodine receptor 1 (RyR1). In isolated mouse muscle fibers, this fragmentation was accompanied by increased SR Ca2+ leak, which can trigger mitochondrial biogenesis. The HIIT-induced RyR1 fragmentation did not occur in muscles exposed to antioxidant, which offers an explanation for why antioxidants blunt effects of endurance training. High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca2+ leak at rest, and depressed force production due to impaired SR Ca2+ release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca2+-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group.

Plasma MicroRNA Levels Differ between Endurance and Strength Athletes

Aim MicroRNAs (miRNAs) are stable in the circulation and are likely to function in inter-organ communication during a variety of metabolic responses that involve changes in gene expression, including exercise training. However, it is unknown whether differences in circulating-miRNA (c-miRNA) levels are characteristic of training modality. Methods We investigated whether levels of candidate c-miRNAs differ between elite male athletes of two different training modalities (n = 10 per group) - endurance (END) and strength (STR) - and between these groups and untrained controls (CON; n = 10). Fasted, non-exercised, morning plasma samples were analysed for 14 c-miRNAs (miR-1, miR-16-2, miR-20a-1, miR-21, miR-93, miR-103a, miR-133a, miR-146a, miR-192, miR-206, miR-221, miR-222, miR-451, miR-499). Moreover, we investigated whether c-miRNA levels were associated with quantitative performance-related phenotypes within and between groups. Results miR-222 was present at different levels in the three participant groups (p = 0.028) with the highest levels being observed in END and the lowest in STR. A number of other c-miRNAs were present at higher levels in END than in STR (relative to STR, ± 1 SEM; miR-222: 1.94 fold (1.73-2.18), p = 0.011; miR-21: 1.56 fold (1.39-1.74), p = 0.013; miR-146a: 1.50 fold (1.38-1.64), p = 0.019; miR-221: 1.51 fold (1.34-1.70), p = 0.026). Regression analyses revealed several associations between candidate c-miRNA levels and strength-related performance measures before and after adjustment for muscle or fat mass, but not following adjustment for group. Conclusion Certain c-miRNAs (miR-222, miR-21, miR-146a and miR-221) differ between endurance- and resistance-trained athletes and thus have potential as useful biomarkers of exercise training and / or play a role in exercise mode-specific training adaptations. However, levels of these c-miRNAs are probably unrelated to muscle bulk or fat reserves.

Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans

Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that exercise protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the kynurenine metabolism away from the neurotoxic kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present study, we investigated the effect of exercise on kynurenine metabolism in humans. KAT gene and protein expression was increased in the muscles of endurance-trained subjects compared with untrained subjects. Endurance exercise caused an increase in plasma KYNA within the first hour after exercise. In contrast, a bout of high-intensity eccentric exercise did not lead to increased plasma KYNA concentration. Our results show that regular endurance exercise causes adaptations in kynurenine metabolism which can have implications for exercise recommendations for patients with depressive disorder.

Human alpha-actinin-3 genotype association with exercise-induced muscle damage and the repeated-bout effect.

Alpha-actinin-3 (ACTN3) is an integral part of the Z line of the sarcomere. The ACTN3 R577X (rs1815739) polymorphism determines the presence or absence of functional ACTN3, which may influence the extent of exercise-induced muscle damage. This study aimed to compare the impact of, and recovery from, muscle-damaging eccentric exercise on subjects with or without functional ACTN3. Seventeen young men (20-33 years old), homozygous for the R (n = 9) or X (n = 8) alleles, performed two bouts of stretch-shortening exercise (50 drop jumps) two weeks apart. Muscle soreness, plasma creatine kinase (CK) activity, jump height, maximal voluntary isometric torque (MVC), peak concentric isokinetic torque (IT), and electrically stimulated knee extension torques at 20 and 100 Hz were measured at baseline and at a number of time points up to 14 days after each bout. There were no significant baseline differences between the groups. However, significant time point × genotype interactions were observed for MVC (p = 0.021) and IT (p = 0.011) for the immediate effect of eccentric exercise in bout 1. The RR group showed greater voluntary force decrements (RR vs. XX: MVC, -33.3% vs. -24.5%; IT, -35.9% vs. -23.2%) and slower recovery. A repeated-bout effect was clearly observed, but there were no differences by genotype group. The ACTN3 genotype modulates the response of muscle function to plyometric jumping exercise, although the differences are modest. The ACTN3 genotype does not influence the clearly observed repeated-bout effect; however, XX homozygotes recover baseline voluntary torque values faster and thus may be able to undertake more frequent training sessions.

Divergent physiological characteristics and responses to endurance training among inbred mouse strains

Both baseline values and adaptive changes in mice can vary depending on the genetic background. We aimed to assess variation in a battery of variables and their adaptations to endurance training in six inbred mouse strains.

Concentric myocardial hypertrophy after one-year of increased training volume in experienced distance runners

Objectives: As evidence on the predominant type of cardiac hypertrophy due to endurance running training is inconsistent, the aim of this study was to investigate the effect of increased training volume on echocardiographic variables of distance runners. Methods: Twenty three adult, experienced, male distance runners underwent standard two dimensionally guided M mode and Doppler echocardiography before and after a one year period during which they were randomly allocated to either control (n  =  11) or intervention (n  =  12) groups. The intervention group increased their training volume from (mean (SD)) 8.0 (3.0) to 12.5 (3.9) hours/week without increasing the intensity, and the controls changed neither training parameter. Results: In the intervention group, training induced an increase in left ventricular (LV) mass (from 240.4 (53.8) to 279.5 (60.6) g, p<0.001) and LV mass index (from 126.7 (28.2) to 147.6 (32.3) g/m2, p<0.001) mainly due to an increase in end diastolic interventricular septum (from 10.4 (1.8) to 11.5 (1.7) mm, p<0.01) and LV posterior wall thickness (from 10.4 (1.6) to 11.5 (1.6) mm, p<0.001). No significant changes in LV internal diameter or measured indices of LV function occurred (p>0.05). The sum of the right ventricular diameter and wall thickness was greater after the increased volume training (p<0.05). None of the variables changed significantly in the control group (p>0.05). Conclusions: In experienced, subelite distance runners, further increasing the training volume results in concentric cardiac hypertrophy.

H55N polymorphism as a likely cause of variation in citrate synthase activity of mouse skeletal muscle

Citrate synthase (CS) is an enzyme of the Krebs cycle that plays a key role in mitochondrial metabolism. The aim of this study was to investigate the mechanisms underlying low activity of citrate synthase (CS) in A/J mice compared with other inbred strains of mice. Enzyme activity, protein content, and mRNA levels of CS were studied in the quadriceps muscles of A/J, BALB/cByJ, C57BL/6J, C3H/HeJ, DBA/2J, and PWD/PhJ strains of mice. Cytochrome c protein content was also measured. The results of the study indicate that A/J mice have a 50-65% reduction in CS activity compared with other strains despite similar levels of Cs mRNA and lack of differences in CS and cytochrome c protein content. CS from A/J mice also showed lower Michaelis constant (K(m)) for both acetyl CoA and oxaloacetate compared with the other strains of mice. In silico analysis of the genomic sequence identified a nonsynonymous single nucleotide polymorphism (SNP) (rs29358506, H55N) in Cs gene occurring near the site of the protein interacting with acetyl CoA. Allelic variants of the polymorphism segregated with the catalytic properties of CS enzyme among the strains. In summary, H55N polymorphism in Cs could be the underlying cause of low CS activity and its high affinity for substrates in A/J mice compared with other strains. This SNP might also play a role in resistance to obesity of A/J mice.

Personality Traits and Exercise Capacity in Male Athletes and Non-Athletes:

To investigate the relationships between personality traits and athletic capacity, this study compared a sample of 376 young adult men (169 athletes, 207 non-athletes; M age = 23.8 yr., SD = 3.9). 26 lab-based exercise capacity parameters were measured, as well as the Big Five major personality traits using the NEO Five-Factor Inventory. The results indicated that athletes scored higher than non-athletes for Conscientiousness but scores were not statistically different between groups for other personality traits. Team sport athletes scored higher on Extraversion than endurance athletes. All the personality traits were associated with some of the exercise capacity indices; however, these correlations were rather weak (rs < .2).

Genetic and genomic analyses of musculoskeletal differences between BEH and BEL strains

Berlin high (BEH) and Berlin low (BEL) strains selected for divergent growth differ threefold in body weight. We aimed at examining muscle mass, which is a major contributor to body weight, by exploring morphological characteristics of the soleus muscle (fiber number and cross sectional area; CSA), by analyzing the transcriptome of the gastrocnemius and by initiating quantitative trait locus (QTL) mapping. BEH muscles were four to eight times larger than those of BEL. In substrain BEH+/+, mutant myostatin was replaced with a wild-type allele; however, BEH+/+muscles still were two to four times larger compared with BEL. BEH soleus muscle fibers were two times more numerous (P < 0.0001) and CSA was two times larger (P < 0.0001) compared with BEL. In addition, soleus femoral attachment anomaly (SFAA) was observed in all BEL mice. One significant (Chr 1) and four suggestive (Chr 3, 4, 6, and 9) muscle weight QTLs were mapped in a 21-day-old F2 intercross (n = 296) between BEH and BEL strains. The frequency of SFAA incidence in the F2 and in the backcross to BEL strain (BCL) suggested the presence of more than one causative gene. Two suggestive SFAA QTLs were mapped in BCL; however, their peak markers were not associated with the phenotype in F2. RNA-Seq analysis revealed 2,148 differentially expressed (P < 0.1) genes and 45,673 single nucleotide polymorphisms and >2,000 indels between BEH+/+ and BEL males. In conclusion, contrasting muscle traits and genomic and gene expression differences between BEH and BEL strains provide a promising model for the search for genes involved in muscle growth and musculoskeletal morphogenesis.

Secular trends in physical fitness and body size in Lithuanian children and adolescents between 1992 and 2012

Background and methods There is a paucity of data on contemporary secular trends on the different aspects of physical fitness in school-aged children and adolescents. This study presents the largest ever data set on changes in fitness between 1992, 2002 and 2012 for both genders of schoolchildren aged 11–18 years (n=16 199). Eurofit test battery was used to assess the balance, flexibility, muscular strength and power, agility and cardiorespiratory fitness. Anthropometrics were also measured and body mass index (BMI) was calculated. Results The study has shown loss of flexibility, leg muscle power, upper body strength and cardiorespiratory fitness between 1992 and 2012, although there was an improvement in abdominal muscle strength in girls, agility in boys and balance in both genders during the same period. At large, negative trends in aspects of fitness seen between 1992 and 2002 have not slowed down between 2002 and 2012. Positive trends in agility and abdominal muscle strength seen before 2002 have regressed or were reversed between 2002 and 2012, while balance continued to improve at increased pace. While the BMI continued to increase in all groups, analysis of covariance has shown that it was not the main cause of changes in fitness. Conclusions The general decline in physical fitness in Lithuanian schoolchildren observed between 1992 and 2002 continued between 2002 and 2012, although some aspects of fitness showed a positive trend. If this general negative trend continues, it will compromise the well-being of future adults and create a serious economic burden on the society.