Mark A. Tarnopolsky

Short‐term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance

Brief, intense exercise training may induce metabolic and performance adaptations comparable to traditional endurance training. However, no study has directly compared these diverse training strategies in a standardized manner. We therefore examined changes in exercise capacity and molecular and cellular adaptations in skeletal muscle after low volume sprint‐interval training (SIT) and high volume endurance training (ET). Sixteen active men (21 ± 1 years, ) were assigned to a SIT or ET group (n= 8 each) and performed six training sessions over 14 days. Each session consisted of either four to six repeats of 30 s ‘all out’ cycling at ∼250% with 4 min recovery (SIT) or 90–120 min continuous cycling at ∼65% (ET). Training time commitment over 2 weeks was ∼2.5 h for SIT and ∼10.5 h for ET, and total training volume was ∼90% lower for SIT versus ET (∼630 versus∼6500 kJ). Training decreased the time required to complete 50 and 750 kJ cycling time trials, with no difference between groups (main effects, P≤ 0.05). Biopsy samples obtained before and after training revealed similar increases in muscle oxidative capacity, as reflected by the maximal activity of cytochrome c oxidase (COX) and COX subunits II and IV protein content (main effects, P≤ 0.05), but COX II and IV mRNAs were unchanged. Training‐induced increases in muscle buffering capacity and glycogen content were also similar between groups (main effects, P≤ 0.05). Given the large difference in training volume, these data demonstrate that SIT is a time‐efficient strategy to induce rapid adaptations in skeletal muscle and exercise performance that are comparable to ET in young active men.

Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men

BACKGROUND The anabolic effect of resistance exercise is enhanced by the provision of dietary protein. OBJECTIVES We aimed to determine the ingested protein dose response of muscle (MPS) and albumin protein synthesis (APS) after resistance exercise. In addition, we measured the phosphorylation of candidate signaling proteins thought to regulate acute changes in MPS. DESIGN Six healthy young men reported to the laboratory on 5 separate occasions to perform an intense bout of leg-based resistance exercise. After exercise, participants consumed, in a randomized order, drinks containing 0, 5, 10, 20, or 40 g whole egg protein. Protein synthesis and whole-body leucine oxidation were measured over 4 h after exercise by a primed constant infusion of [1-(13)C]leucine. RESULTS MPS displayed a dose response to dietary protein ingestion and was maximally stimulated at 20 g. The phosphorylation of ribosomal protein S6 kinase (Thr(389)), ribosomal protein S6 (Ser(240/244)), and the epsilon-subunit of eukaryotic initiation factor 2B (Ser(539)) were unaffected by protein ingestion. APS increased in a dose-dependent manner and also reached a plateau at 20 g ingested protein. Leucine oxidation was significantly increased after 20 and 40 g protein were ingested. CONCLUSIONS Ingestion of 20 g intact protein is sufficient to maximally stimulate MPS and APS after resistance exercise. Phosphorylation of candidate signaling proteins was not enhanced with any dose of protein ingested, which suggested that the stimulation of MPS after resistance exercise may be related to amino acid availability. Finally, dietary protein consumed after exercise in excess of the rate at which it can be incorporated into tissue protein stimulates irreversible oxidation.

Gender differences in strength and muscle fiber characteristics

SummaryStrength and muscle characteristics were examined in biceps brachii and vastus lateralis of eight men and eight women. Measurements included motor unit number, size and activation and voluntary strength of the elbow flexors and knee extensors. Fiber areas and type were determined from needle biopsies and muscle areas by computerized tomographical scanning. The women were approximately 52% and 66% as strong as the men in the upper and lower body respectively. The men were also stronger relative to lean body mass. A significant correlation was found between strength and muscle cross-sectional area (CSA; P≤0.05). The women had 45, 41, 30 and 25% smaller muscle CSAs for the biceps brachii, total elbow flexors, vastus lateralis and total knee extensors respectively. The men had significantly larger type I fiber areas (4597 vs 3483 μm2) and mean fiber areas (6632 vs 3963 μm2) than the women in biceps brachii and significantly larger type II fiber areas (7700 vs 4040 μm2) and mean fiber areas (7070 vs 4290 μm2) in vastus lateralis. No significant gender difference was found in the strength to CSA ratio for elbow flexion or knee extension, in biceps fiber number (180 620 in men vs 156 872 in women), muscle area to fiber area ratio in the vastus lateralis 451 468 vs 465 007) or any motor unit characteristics. Data suggest that the greater strength of the men was due primarily to larger fibers. The greater gender difference in upper body strength can probably be attributed to the fact that women tend to have a lower proportion of their lean tissue distributed in the upper body. It is difficult to determine the extent to which the larger fibers in men represent a true biological difference rather that a difference in physical activity, but these data suggest that it is largely an innate gender difference.

Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men

This study was designed to compare the acute response of mixed muscle protein synthesis (MPS) to rapidly (i.e., whey hydrolysate and soy) and slowly (i.e., micellar casein) digested proteins both at rest and after resistance exercise. Three groups of healthy young men (n = 6 per group) performed a bout of unilateral leg resistance exercise followed by the consumption of a drink containing an equivalent content of essential amino acids (10 g) as either whey hydrolysate, micellar casein, or soy protein isolate. Mixed MPS was determined by a primed constant infusion of l-[ring-(13)C(6)]phenylalanine. Ingestion of whey protein resulted in a larger increase in blood essential amino acid, branched-chain amino acid, and leucine concentrations than either casein or soy (P < 0.05). Mixed MPS at rest (determined in the nonexercised leg) was higher with ingestion of faster proteins (whey = 0.091 +/- 0.015, soy = 0.078 +/- 0.014, casein = 0.047 +/- 0.008%/h); MPS after consumption of whey was approximately 93% greater than casein (P < 0.01) and approximately 18% greater than soy (P = 0.067). A similar result was observed after exercise (whey > soy > casein); MPS following whey consumption was approximately 122% greater than casein (P < 0.01) and 31% greater than soy (P < 0.05). MPS was also greater with soy consumption at rest (64%) and following resistance exercise (69%) compared with casein (both P < 0.01). We conclude that the feeding-induced simulation of MPS in young men is greater after whey hydrolysate or soy protein consumption than casein both at rest and after resistance exercise; moreover, despite both being fast proteins, whey hydrolysate stimulated MPS to a greater degree than soy after resistance exercise. These differences may be related to how quickly the proteins are digested (i.e., fast vs. slow) or possibly to small differences in leucine content of each protein.

Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle.

Resistance (RE) and endurance (EE) exercise stimulate mixed skeletal muscle protein synthesis. The phenotypes induced by RE (myofibrillar protein accretion) and EE (mitochondrial expansion) training must result from differential stimulation of myofibrillar and mitochondrial protein synthesis. We measured the synthetic rates of myofibrillar and mitochondrial proteins and the activation of signalling proteins (Akt–mTOR–p70S6K) at rest and after an acute bout of RE or EE in the untrained state and after 10 weeks of RE or EE training in young healthy men. While untrained, RE stimulated both myofibrillar and mitochondrial protein synthesis, 67% and 69% (P < 0.02), respectively. After training, only myofibrillar protein synthesis increased with RE (36%, P= 0.05). EE stimulated mitochondrial protein synthesis in both the untrained, 154%, and trained, 105% (both P < 0.05), but not myofibrillar protein synthesis. Acute RE and EE increased the phosphorylation of proteins in the Akt–mTOR–p70S6K pathway with comparatively minor differences between two exercise stimuli. Phosphorylation of Akt–mTOR–p70S6K proteins was increased after 10 weeks of RE training but not by EE training. Chronic RE or EE training modifies the protein synthetic response of functional protein fractions, with a shift toward exercise phenotype‐specific responses, without an obvious explanatory change in the phosphorylation of regulatory signalling pathway proteins.

A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms

High‐intensity interval training (HIT) induces skeletal muscle metabolic and performance adaptations that resemble traditional endurance training despite a low total exercise volume. Most HIT studies have employed ‘all out’, variable‐load exercise interventions (e.g. repeated Wingate tests) that may not be safe, practical and/or well tolerated by certain individuals. Our purpose was to determine the performance, metabolic and molecular adaptations to a more practical model of low‐volume HIT. Seven men (21 ± 0.4 years, ml kg−1 min−1) performed six training sessions over 2 weeks. Each session consisted of 8–12 × 60 s intervals at ∼100% of peak power output elicited during a ramp peak test (355 ± 10 W) separated by 75 s of recovery. Training increased exercise capacity, as assessed by significant improvements on both 50 kJ and 750 kJ cycling time trials (P < 0.05 for both). Skeletal muscle (vastus lateralis) biopsy samples obtained before and after training revealed increased maximal activity of citrate synthase (CS) and cytochrome c oxidase (COX) as well as total protein content of CS, COX subunits II and IV, and the mitochondrial transcription factor A (Tfam) (P < 0.05 for all). Nuclear abundance of peroxisome proliferator‐activated receptor γ co‐activator 1α (PGC‐1α) was ∼25% higher after training (P < 0.05), but total PGC‐1α protein content remained unchanged. Total SIRT1 content, a proposed activator of PGC‐1α and mitochondrial biogenesis, was increased by ∼56% following training (P < 0.05). Training also increased resting muscle glycogen and total GLUT4 protein content (both P < 0.05). This study demonstrates that a practical model of low volume HIT is a potent stimulus for increasing skeletal muscle mitochondrial capacity and improving exercise performance. The results also suggest that increases in SIRT1, nuclear PGC‐1α, and Tfam may be involved in coordinating mitochondrial adaptations in response to HIT in human skeletal muscle.

Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes

Low-volume high-intensity interval training (HIT) is emerging as a time-efficient exercise strategy for improving health and fitness. This form of exercise has not been tested in type 2 diabetes and thus we examined the effects of low-volume HIT on glucose regulation and skeletal muscle metabolic capacity in patients with type 2 diabetes. Eight patients with type 2 diabetes (63 ± 8 yr, body mass index 32 ± 6 kg/m(2), Hb(A1C) 6.9 ± 0.7%) volunteered to participate in this study. Participants performed six sessions of HIT (10 × 60-s cycling bouts eliciting ∼90% maximal heart rate, interspersed with 60 s rest) over 2 wk. Before training and from ∼48 to 72 h after the last training bout, glucose regulation was assessed using 24-h continuous glucose monitoring under standardized dietary conditions. Markers of skeletal muscle metabolic capacity were measured in biopsy samples (vastus lateralis) before and after (72 h) training. Average 24-h blood glucose concentration was reduced after training (7.6 ± 1.0 vs. 6.6 ± 0.7 mmol/l) as was the sum of the 3-h postprandial areas under the glucose curve for breakfast, lunch, and dinner (both P < 0.05). Training increased muscle mitochondrial capacity as evidenced by higher citrate synthase maximal activity (∼20%) and protein content of Complex II 70 kDa subunit (∼37%), Complex III Core 2 protein (∼51%), and Complex IV subunit IV (∼68%, all P < 0.05). Mitofusin 2 (∼71%) and GLUT4 (∼369%) protein content were also higher after training (both P < 0.05). Our findings indicate that low-volume HIT can rapidly improve glucose control and induce adaptations in skeletal muscle that are linked to improved metabolic health in patients with type 2 diabetes.

Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise

To search for novel transcriptional pathways that are activated in skeletal muscle after endurance exercise, we used cDNA microarrays to measure global mRNA expression after an exhaustive bout of high‐intensity cycling (∼75 min). Healthy, young, sedentary males performed the cycling bout, and skeletal muscle biopsies were taken from the vastus lateralis before, and at 3 and 48 h after exercise. We examined mRNA expression in individual muscle samples from four subjects using cDNA microarrays, used repeated‐measures significance analysis of microarray (SAM) to determine statistically significant expression changes, and confirmed selected results using real‐time RT‐PCR. In total, the expression of 118 genes significantly increased 3 h postcycling and 8 decreased. At 48 h, the expression of 29 genes significantly increased and 5 decreased. Many of these are potentially important novel genes involved in exercise recovery and adaptation, including several involved in 1) metabolism and mitochondrial biogenesis (FOXO1, PPARδ, PPARγ, nuclear receptor binding protein 2, IL‐6 receptor, ribosomal protein L2, aminolevulinate δ‐synthase 2); 2) the oxidant stress response (metalothioneins 1B, 1F, 1G, 1H, 1L, 2A, 3, interferon regulatory factor 1); and 3) electrolyte transport across membranes [Na+‐K+‐ATPase (β3), SERCA3, chloride channel 4]. Others include genes involved in cell stress, proteolysis, apoptosis, growth, differentiation, and transcriptional activation, as well as all three nuclear receptor subfamily 4A family members (Nur77, Nurr1, and Nor1). This study is the first to characterize global mRNA expression during recovery from endurance exercise, and the results provide potential insight into 1) the transcriptional contributions to homeostatic recovery in human skeletal muscle after endurance exercise, and 2) the transcriptional contributions from a single bout of endurance exercise to the adaptive processes that occur after a period of endurance exercise training.

Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion

We tested the hypothesis that increasing blood amino acid (AA) availability would counter the physical inactivity‐induced reduction in muscle protein synthesis. We determined how 14 days of unilateral knee immobilization affected quadriceps myofibrillar protein synthesis (MPS) in young healthy subjects (10 men, 2 women, 21 ± 1 years; 80.2 ± 4.0 kg, mean ±s.e.m.) in the post‐absorptive state and after infusing AA (10% Primene) at low or high doses (43 and 261 mg kg−1 h−1). Muscle cross‐sectional area (MRI) and peak isometric torque declined in the immobilized leg (−5.0 ± 1.2% and −25 ± 3%, respectively, both P < 0.005), but were unchanged (all P > 0.6) in the non‐immobilized leg. Immobilization induced a 27% decline in the rate of post‐absorptive MPS (immobilized, 0.027 ± 0.003: non‐immobilized, 0.037 ± 0.003% h−1; P < 0.001). Regardless of dose, AA infusion stimulated a greater rise in MPS in the non‐immobilized legs; at 4 h MPS was greater by +54 ± 12% with low dose and +68 ± 17% with high dose AA infusion (both P < 0.001). There was some evidence of delayed responsiveness of phosphorylation of Akt to high doses of AA and p70S6k at both doses but no marked differences in that of mTOR, GSK3β or eEF2. Phosphorylation of focal adhesion kinase (Tyr576/577) was reduced (P < 0.05) with immobilization. We observed no change in polyubiquitinated protein content after immobilization. We confirm that 14 days of immobilization reduces MPS in the post‐absorptive state and this diminution is reduced but not abolished by increased provision of AA, even at high rates. The immobilization‐induced decline in post‐absorptive MPS with the ‘anabolic resistance’ to amino acids can account for much of immobilization‐induced muscle atrophy.

Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men.

Feeding stimulates robust increases in muscle protein synthesis (MPS); however, ageing may alter the anabolic response to protein ingestion and the subsequent aminoacidaemia. With this as background, we aimed to determine in the present study the dose-response of MPS with the ingestion of isolated whey protein, with and without prior resistance exercise, in the elderly. For the purpose of this study, thirty-seven elderly men (age 71 (sd 4) years) completed a bout of unilateral leg-based resistance exercise before ingesting 0, 10, 20 or 40 g of whey protein isolate (W0-W40, respectively). Infusion of l-[1-13C]leucine and l-[ring-13C6]phenylalanine with bilateral vastus lateralis muscle biopsies were used to ascertain whole-body leucine oxidation and 4 h post-protein consumption of MPS in the fed-state of non-exercised and exercised leg muscles. It was determined that whole-body leucine oxidation increased in a stepwise, dose-dependent manner. MPS increased above basal, fasting values by approximately 65 and 90 % for W20 and W40, respectively (P < 0·05), but not with lower doses of whey. While resistance exercise was generally effective at stimulating MPS, W20 and W40 ingestion post-exercise increased MPS above W0 and W10 exercised values (P < 0·05) and W40 was greater than W20 (P < 0·05). Based on the study, the following conclusions were drawn. At rest, the optimal whey protein dose for non-frail older adults to consume, to increase myofibrillar MPS above fasting rates, was 20 g. Resistance exercise increases MPS in the elderly at all protein doses, but to a greater extent with 40 g of whey ingestion. These data suggest that, in contrast to younger adults, in whom post-exercise rates of MPS are saturated with 20 g of protein, exercised muscles of older adults respond to higher protein doses.