Ted Österlund

Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes

Alpha-actinins are structural proteins of the Z-line. Human skeletal muscle expresses two alpha-actinin isoforms, alpha-actinin-2 and alpha-actinin-3, encoded by their respective genes ACTN2 and ACTN3. ACTN2 is expressed in all muscle fiber types, while only type II fibers, and particularly the type IIb fibers, express ACTN3. ACTN3 (R577X) polymorphism results in loss of alpha-actinin-3 and has been suggested to influence skeletal muscle function. The X allele is less common in elite sprint and power athletes than in the general population and has been suggested to be detrimental for performance requiring high power. The present study investigated the association of ACTN3 genotype with muscle power during 30-s Wingate cycling in 120 moderately to well-trained men and women and with knee extensor strength and fatigability in a subset of 21 men performing isokinetic exercise. Muscle biopsies were obtained from the vastus lateralis muscle to determine fiber-type composition and ACTN2 and ACTN3 mRNA levels. Peak and mean power and the torque-velocity relationship and fatigability output showed no difference across ACTN3 genotypes. Thus this study suggests that R577X polymorphism in ACTN3 is not associated with differences in power output, fatigability, or force-velocity characteristics in moderately trained individuals. However, repeated exercise bouts prompted an increase in peak torque in RR but not in XX genotypes, suggesting that ACTN3 genotype may modulate responsiveness to training. Our data further suggest that alpha-actinins do not play a significant role in determining muscle fiber-type composition. Finally, we show that ACTN2 expression is affected by the content of alpha-actinin-3, which implies that alpha-actinin-2 may compensate for the lack of alpha-actinin-3 and hence counteract the phenotypic consequences of the deficiency.

Effects of 3 days unloading on molecular regulators of muscle size in humans

Changes in skeletal muscle mass are controlled by mechanisms that dictate protein synthesis or degradation. The current human study explored whether changes in activation of the phosphoinositide 3-kinase (PI3K)-Akt1, p38, myostatin, and mRNA expression of markers of protein degradation and synthesis occur soon after withdrawal of weight bearing. Biopsies of the vastus lateralis muscle (VL) and soleus muscle (Sol) were obtained from eight healthy men before and following 3 days of unilateral lower limb suspension (ULLS). Akt1, Forkhead box class O (FOXO)-1A, FOXO-3A, p38, and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) phosphorylation and protein levels and myostatin protein level were analyzed by Western blot. Levels of mRNA of IGF1, FOXO-1A, FOXO-3A, atrogin-1, MuRF-1, caspase-3, calpain-2, calpain-3, 4E-BP1, and myostatin were measured using real-time PCR. The amounts of phosphorylated Akt1, FOXO-1A, FOXO-3A, and p38 were unaltered (P>0.05) after ULLS. Similarly, mRNA levels of IGF1, FOXO-1A, FOXO-3A, caspase-3, calpain-2, and calpain-3 showed no changes (P>0.05). The mRNA levels of atrogin-1 and MuRF-1, as well as the mRNA and protein phosphorylation of 4E-BP1, increased (P<0.05) in VL but not in Sol. Both muscles showed increased (P<0.05) myostatin mRNA and protein following ULLS. These results suggest that pathways other than PI3K-Akt stimulate atrogin-1 and MuRF-1 expression within 3 days of ULLS. Alternatively, transient changes in these pathways occurred in the early phase of ULLS. The increased myostatin mRNA and protein expression also indicate that multiple processes are involved in the early phase of muscle wasting. Further, the reported difference in gene expression pattern across muscles suggests that mechanisms regulating protein content in human skeletal muscle are influenced by phenotype and/or function.

Sprint exercise enhances skeletal muscle p70S6k phosphorylation and more so in women than in men.

Sprint exercise is characterized by repeated sessions of brief intermittent exercise at a high relative workload. However, little is known about the effect on mTOR pathway, an important link in the regulation of muscle protein synthesis. An earlier training study showed a greater increase in muscle fibre cross‐sectional area in women than men. Therefore, we tested the hypothesis that the activation of mTOR signalling is more pronounced in women than in men. Healthy men (n = 9) and women (n = 8) performed three bouts of 30‐s sprint exercise with 20‐min rest in between.

ACTN3 genotype and modulation of skeletal muscle response to exercise in human subjects.

α-Actinin-3 is a Z-disc protein expressed only in type II muscle fibers. A polymorphism in the ACTN3 gene (R577X) results in lack of α-actinin-3 in XX genotype. The prevalence of the mutated X-allele is lower among power/sprint oriented athletes compared with controls, indicating that the lack of α-actinin-3 is detrimental in these sports, but a mechanistic link has not been established. Results from Actn3-knockout (KO) mouse model suggest that α-actinin-3 may affect muscle mass and muscle glycogen levels. In the present investigation we examined muscle fiber type composition, cross-sectional fiber area (CSA), and muscle glycogen levels at baseline in 143 human subjects with different ACTN3 genotypes. In addition, hypertrophy signaling and glycogen utilization in response to sprint exercise were studied in a subset of subjects. Glycogen utilization was analyzed in separate pools of type I and type II fibers. No differences in fiber type composition, CSA, or muscle glycogen levels were observed at baseline across the ACTN3 genotypes. However, the sprint exercise-induced increase in phosphorylation of mTOR and p70S6k was smaller in XX than in RR+RX (P = 0.03 and P = 0.01, respectively), indicating a less pronounced activation of hypertrophy signaling in XX. Glycogen utilization during sprint exercise varied across ACTN3 genotypes in type II fibers (P = 0.03) but not in type I fibers (P = 0.38). The present results are in accordance with findings from the KO mice and reinforce the hypothesis that ACTN3 genotype-associated differences in muscle mass and glycogen utilization provide a mechanistic explanation for the modulation of human performance by the ACTN3 genotype.

Influence of nutrient ingestion on amino acid transporters and protein synthesis in human skeletal muscle after sprint exercise

Nutrient ingestion is known to increase the exercise-induced stimulation of muscle protein synthesis following resistance exercise. Less is known about the effect of nutrients on muscle protein synthesis following sprint exercise. At two occasions separated by 1 mo, 12 healthy subjects performed three 30-s sprints with 20-min rest between bouts. In randomized order, they consumed a drink with essential amino acids and maltodextrin (nutrient) or flavored water (placebo). Muscle biopsies were obtained 80 and 200 min after the last sprint, and blood samples were taken repeatedly during the experiment. Fractional synthetic rate (FSR) was measured by continuous infusion of l-[2H5]phenylalanine up to 200 min postexercise. The mRNA expression and protein expression of SNAT2 were both 1.4-fold higher ( P < 0.05) after nutrient intake compared with placebo at 200 min postexercise. Phosphorylated Akt, mammalian target of rapamycin (mTOR), and p70S6k were 1.7- to 3.6-fold higher ( P < 0.01) 80 min after the last sprint with nutrient ingestion as compared with placebo. In addition, FSR was higher ( P < 0.05) with nutrients when plasma phenylalanine (FSRplasma) was used as a precursor but not when intracellular phenylalanine (FSRmuscle) was used. Significant correlations were also found between FSRplasma on the one hand and plasma leucine and serum insulin on the other hand in the nutrient condition. The results show that nutrient ingestion induces the expression of the amino acid transporter SNAT2 stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis following sprint exercise. NEW & NOTEWORTHY There is limited knowledge regarding the effect of nutrients on muscle protein synthesis following sprint as compared with resistance exercise. The results demonstrate that nutrient ingestion during repeated 30-s bouts of sprint exercise induces expression of the amino acid transporter SNAT2 and stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis. Future studies to explore the chronic effects of nutritional ingestion during sprint exercise sessions on muscle mass accretion are warranted.

Amino Acid Transport after Sprint Exercise and Oral Amino Acids : 90 Board #6 June 1, 9

PURPOSE: To study if oral ingestion of essential amino acids (oral EAA) increases the amino acid transporter SNAT2, Akt/mTOR signaling and muscle protein synthesis (MPS) after sprint exercise.METHO ...