Interrupting prolonged sitting with repeated chair stands or short walks reduces postprandial insulinemia in healthy adults.

We determined if interrupting prolonged sitting with practical "activity snacks" could reduce postprandial glycemia and insulinemia in healthy adults. Fourteen participants (7 males, 7 females; 24 ± 5 yr; 25 ± 5 kg/m2; 40 ± 8 mL/kg/min; 7,033 ± 2,288 steps/day) completed three 7.5-h trials in a randomized order consisting of uninterrupted sitting (SIT), sitting with intermittent (every 30 min) walking (WALK; 2 min at 3.1 mph), or sitting with intermittent squats (SQUAT; 15 chair stands with calf raise). Mixed-macronutrient liquid meals provided 20% ("breakfast") and 30% ("lunch") of daily energy needs to mimic Western meal patterns. Blood samples were obtained for analysis of postprandial plasma glucose and insulin concentrations, and skeletal muscle biopsy samples were collected to measure markers of contraction- and insulin-mediated glucose uptake signaling. Postprandial glucose and insulin did not differ across conditions following breakfast. After lunch, peak insulin concentration was lower in SQUAT (52 ± 27, P < 0.01) and WALK (62 ± 35, P < 0.05) compared with SIT (79 ± 43 µIU/mL). The insulin incremental area under the curve (iAUC) 1 h following lunch was 37 and 29% lower in SQUAT (P < 0.01) and WALK (P < 0.05) compared with SIT, respectively; however, 3-h insulin iAUC was reduced in SQUAT only (24% vs. SIT, P < 0.05). The 3-h insulin:glucose iAUC was reduced following lunch in both SQUAT (30%) and WALK (23%) compared with SIT (P < 0.05). Phosphorylation of AKTThr308, AKTSer473, and AS160Ser318 was not different between conditions (P > 0.05). Interrupting prolonged sitting with short walks or repeated chair stands reduces postprandial insulinemia in healthy adults. Our results may have implications for mitigating cardiometabolic disease risk in adults who engage in periods of prolonged sitting.NEW & NOTEWORTHY Breaking up prolonged sitting with intermittent walking breaks can improve glycemic control. Here, we demonstrated that interrupting prolonged sitting every 30 min with 1 min of repeated chair stands was as effective as 2-min treadmill walks for lowering postprandial insulinemia in healthy adults. Markers of contraction- and insulin-mediated muscle glucose uptake were unchanged. Repeated chair stands as a form of body-weight resistance activity may represent a cost- and space-efficient activity break for mitigating cardiometabolic-disease risk.

Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients.

INTRODUCTION: Skeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy. METHODS: Eight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m2) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m2) received primed continuous L-[ring-2H5]phenylalanine and L-[1-13C]leucine infusions with blood and muscle biopsy sampling on a nondialysis day. Participants consumed a mixed meal (546 kcal; 20-g protein, 59-g carbohydrates, 26-g fat) with protein provided as L-[5,5,5-2H3]leucine-labeled eggs. RESULTS: Circulating dietary amino acid availability was reduced in MHD patients (41 ± 5%) versus control subjects (61 ± 4%; P = 0.03). Basal muscle caspase-3 protein content was elevated (P = 0.03) and large neutral amino acid transporter 1 (LAT1) protein content was reduced (P = 0.02) in MHD patients versus control subjects. Basal muscle protein synthesis (MPS) was ∼2-fold higher in MHD patients (0.030 ± 0.005%/h) versus control subjects (0.014 ± 0.003%/h) (P = 0.01). Meal ingestion failed to increase MPS in MHD patients (absolute change from basal: 0.0003 ± 0.007%/h), but stimulated MPS in control subjects (0.009 ± 0.002%/h; P = 0.004). CONCLUSIONS: MHD patients demonstrated muscle anabolic resistance to meal ingestion. This blunted postprandial MPS response in MHD patients might be related to high basal MPS, which results in a stimulatory ceiling effect and/or reduced plasma dietary amino acid availability after mixed-meal ingestion.

Low-load resistance exercise during inactivity is associated with greater fibre area and satellite cell expression in older skeletal muscle.

BACKGROUND: Age-related sarcopenia is accelerated by physical inactivity. Low-load resistance exercise (LLRE) counters inactivity-induced muscle atrophy in older adults, but changes in muscle fibre morphology are unstudied. We aimed to determine the impact of LLRE during short-term inactivity (step-reduction) on muscle fibre size and capillarity as well as satellite cell (SC) content in older skeletal muscle. METHODS: Fourteen older (~71 years) male adults underwent 14 days of step reduction (<1500 steps/day) while performing six sessions of LLRE (~30% maximal strength) with one leg (SR + EX) while the contralateral leg served as an untrained control (SR). Seven healthy ambulatory age-matched male adults (~69 years) served as a comparator group (COM). Muscle biopsies were taken from the vastus lateralis after 14 days, and immunohistochemical analysis was performed to determine muscle fibre cross-sectional area (CSA), myonuclear content, SC content (PAX7+ cells), and total (C:F) and fibre type-specific (C:Fi) capillary-to-fibre ratios. RESULTS: Type I and II fibre CSA was greater in SR + EX compared with SR. Whereas there were no differences across fibre types between SR + EX and CON, type II fibre CSA was significantly lower in SR compared with COM. Type II myonuclear domain was greater in SR + EX compared with COM and SR. Pax7+ cells associated with type I and II fibres were lower in SR compared with SR + EX. Type II PAX7+ cells were also lower in SR compared with COM with a similar trend for type I fibres. There were trends for a lower C:Fi in SR compared with SR + EX for both fibre types with no differences for each compared with COM. CONCLUSIONS: Minimal LLRE during a period of decreased physical activity is associated with greater muscle fibre CSA, SC content, and capillarization. These results support the use of LLRE as an effective countermeasure to inactivity-induced alterations in muscle morphology with age.

Consumption of whole eggs promotes greater stimulation of postexercise muscle protein synthesis than consumption of isonitrogenous amounts of egg whites in young men.

Background: Protein in the diet is commonly ingested from whole foods that contain various macro- and micronutrients. However, the effect of consuming protein within its natural whole-food matrix on postprandial protein metabolism remains understudied in humans.Objective: We aimed to compare the whole-body and muscle protein metabolic responses after the consumption of whole eggs with egg whites during exercise recovery in young men.Design: In crossover trials, 10 resistance-trained men [aged 21 ± 1 y; 88 ± 3 kg; body fat: 16% ± 1% (means ± SEMs)] received primed continuous l-[ring-2H5]phenylalanine and l-[1-13C]leucine infusions and performed a single bout of resistance exercise. After exercise, participants consumed intrinsically l-[5,5,5-2H3]leucine-labeled whole eggs (18 g protein, 17 g fat) or egg whites (18 g protein, 0 g fat). Repeated blood and muscle biopsy samples were collected to assess whole-body leucine kinetics, intramuscular signaling, and myofibrillar protein synthesis.Results: Plasma appearance rates of protein-derived leucine were more rapid after the consumption of egg whites than after whole eggs (P = 0.01). Total plasma availability of leucine over the 300-min postprandial period was similar (P= 0.75) between the ingestion of whole eggs (68% ± 1%) and egg whites (66% ± 2%), with no difference in whole-body net leucine balance (P = 0.27). Both whole-egg and egg white conditions increased the phosphorylation of mammalian target of rapamycin complex 1, ribosomal protein S6 kinase 1, and eukaryotic translation initiation factor 4E-binding protein 1 during postexercise recovery (all P < 0.05). However, whole-egg ingestion increased the postexercise myofibrillar protein synthetic response to a greater extent than did the ingestion of egg whites (P= 0.04).Conclusions: We show that the ingestion of whole eggs immediately after resistance exercise resulted in greater stimulation of myofibrillar protein synthesis than did the ingestion of egg whites, despite being matched for protein content in young men. Our data indicate that the ingestion of nutrient- and protein-dense foods differentially stimulates muscle anabolism compared with protein-dense foods. This trial was registered at clinicaltrials.gov as NCT03117127.

Kinetics of circulating progenitor cell mobilization during submaximal exercise.

Circulating progenitor cells (CPCs) are a heterogeneous population of stem/progenitor cells in peripheral blood that includes hematopoietic stem and progenitor cells (HSPCs and HSCs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs) that are involved in tissue repair and adaptation. CPC mobilization during exercise remains uncharacterized in young adults. The purpose of this study was to investigate the kinetics of CPC mobilization during and after submaximal treadmill running and their relationship to mobilization factors. Seven men [age = 25.3 ± 2.4 yr, body mass index = 23.5 ± 1.0 kg/m2, peak O2 uptake (V̇o2peak) = 60.9 ± 2.74 ml·kg-1·min-1] ran on a treadmill for 60 min at 70% V̇o2peak Blood sampling occurred before (Pre), during [20 min (20e), 40 min (40e), 60 min (60e)], and after exercise [15 min (15p), 60 min (60p), 120 min (120p)] for quantification of CPCs (CD34+), HSPCs (CD34+/CD45low), HSCs (CD34+/CD45low/CD38-), CD34+ MSCs (CD45-/CD34+/CD31-/CD105+), CD34- MSCs (CD45-/CD34-/CD31-/CD105+), and EPCs (CD45-/CD34+/CD31+) via flow cytometry. CPC concentration increased compared with Pre at 20e and 40e (2.7- and 2.4-fold, respectively, P < 0.05). HSPCs and HSCs increased at 20e compared with 60p (2.7- and 2.8-fold, respectively, P < 0.05), whereas EPCs and both MSC populations did not change. CXC chemokine ligand (CXCL) 12 (1.5-fold; P < 0.05) and stem cell factor (1.3-fold; P < 0.05) were increased at 40e and remained elevated postexercise. The peak increase in CPCs was positively correlated to concentration of endothelial cells during exercise with no relationship to CXCL12 and SCF. Our data show the kinetics of progenitor cell mobilization during exercise that could provide insight into cellular mediators of exercise-induced adaptations, and have implication for the use of exercise as an adjuvant therapy for CPC collection in hematopoietic stem cell transplant.NEW & NOTEWORTHY Using a comprehensive evaluation of circulating progenitor cells (CPCs), we show that CPC mobilization during exercise is related to tissue damage, and not plasma concentrations of CXC chemokine ligand 12 and stem cell factor. These data have implications for the use of exercise interventions as adjuvant therapy for CPC mobilization in the context of hematopoietic stem cell transplant and also support the role of mobilized progenitor cells as cellular mediators of systemic adaptations to exercise.

Modulation of autophagy signaling with resistance exercise and protein ingestion following short-term energy deficit.

Autophagy contributes to remodeling of skeletal muscle and is sensitive to contractile activity and prevailing energy availability. We investigated changes in targeted genes and proteins with roles in autophagy following 5 days of energy balance (EB), energy deficit (ED), and resistance exercise (REX) after ED. Muscle biopsies from 15 subjects (8 males, 7 females) were taken at rest following 5 days of EB [45 kcal·kg fat free mass (FFM)(-1)·day(-1)] and 5 days of ED (30 kcal·kg FFM(-1)·day(-1)). After ED, subjects completed a bout of REX and consumed either placebo (PLA) or 30 g whey protein (PRO) immediately postexercise. Muscle biopsies were obtained at 1 and 4 h into recovery in each trial. Resting protein levels of autophagy-related gene protein 5 (Atg5) decreased after ED compared with EB (∼23%, P < 0.001) and remained below EB from 1 to 4 h postexercise in PLA (∼17%) and at 1 h in PRO (∼18%, P < 0.05). In addition, conjugated Atg5 (cAtg12) decreased below EB in PLA at 4 h (∼20, P < 0.05); however, its values were increased above this time point in PRO at 4 h alongside increases in FOXO1 above EB (∼22-26%, P < 0.05). Notably, these changes were subsequent to increases in unc-51-like kinase 1(Ser757) phosphorylation (∼60%) 1 h postexercise in PRO. No significant changes in gene expression of selected autophagy markers were found, but EGR-1 increased above ED and EB in PLA (∼417-864%) and PRO (∼1,417-2,731%) trials 1 h postexercise (P < 0.001). Postexercise protein availability, compared with placebo, can selectively promote autophagic responses to REX in ED.

Canine olfaction and electronic nose detection of volatile organic compounds in the detection of cancer: a review.

Olfactory cancer detection shows promise as an affordable, precise, and noninvasive way to screen for cancer. This review focuses on two methods of olfactory cancer detection: first, the ability of canines to differentiate between cancerous and healthy individuals through the use of biological samples and second, electronic nose technology that uses chemical sensors to detect known biomarkers in exhaled breath. This review summarizes and critiques past research and outlines future directions to improve understanding of both canine olfaction and electronic nose technology.

Keeping older muscle "young" through dietary protein and physical activity.

Sarcopenia is characterized by decreases in both muscle mass and muscle function. The loss of muscle mass, which can precede decrements in muscle function, is ultimately rooted in an imbalance between the rates of muscle protein synthesis and breakdown that favors a net negative balance (i.e., synthesis < breakdown). A preponderance of evidence highlights a blunted muscle protein synthetic response to dietary protein, commonly referred to as "anabolic resistance," as a major underlying cause of the insipid loss of muscle with age. Dietary strategies to overcome this decreased dietary amino acid sensitivity include the ingestion of leucine-enriched, rapidly digested proteins and/or greater protein ingestion in each main meal to maximally stimulate muscle anabolism. Anabolic resistance is also a hallmark of a sedentary lifestyle at any age. Given that older adults may be more likely to experience periods of reduced activity (either voluntarily or through acute illness), it is proposed that inactivity is the precipitating factor in the development of anabolic resistance and the subsequent progression from healthy aging to frailty. However, even acute bouts of activity can restore the sensitivity of older muscle to dietary protein. Provided physical activity is incorporated into the daily routine, muscle in older adults should retain its capacity for a robust anabolic response to dietary protein comparable to that in their younger peers. Therefore, through its ability to "make nutrition better," physical activity should be viewed as a vital component to maintaining muscle mass and function with age.

Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men.

We aimed to determine the effect of consuming pure isolated micellar casein or pure whey protein isolate on rates of myofibrillar protein synthesis (MPS) at rest and after resistance exercise in elderly men. Healthy elderly men (72 (sem 1) years; BMI 26·4 (sem 0·7) kg/m²) were divided into two groups (n 7 each) who received a primed, constant infusion of l-[ring-¹³C6]phenylalanine to measure MPS at rest and during 4 h of exercise recovery. Participants performed unilateral leg resistance exercise followed by the consumption of isonitrogenous quantities (20 g) of casein or whey. Blood essential amino acids and leucine concentration peaked 60 min post-drink and were greater in amplitude after whey protein ingestion (both, P < 0·05). MPS in the rested leg was 65 % higher (P = 0·002) after ingestion of whey (0·040 (sem 0·003) %/h) when compared with micellar casein (0·024 (sem 0·002) %/h). Similarly, resistance exercise-stimulated rates of MPS were greater (P < 0·001) after whey ingestion (0·059 (sem 0·005) %/h) v. micellar casein (0·035 (sem 0·002) %/h). We conclude that ingestion of isolated whey protein supports greater rates of MPS than micellar casein both at rest and after resistance exercise in healthy elderly men. This result is probably related to a greater hyperaminoacidaemia or leucinaemia with whey ingestion.

Rapid aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise.

BACKGROUND: Ingestion of whey or casein yields divergent patterns of aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents. OBJECTIVE: Our objective was to determine the effect of divergent aminoacidemia by manipulating ingestion patterns of whey protein alone on MPS and anabolic signaling after resistance exercise. DESIGN: In separate trials, 8 healthy men consumed whey protein either as a single bolus (BOLUS; 25-g dose) or as repeated, small, "pulsed" drinks (PULSE; ten 2.5-g drinks every 20 min) to mimic a more slowly digested protein. MPS and phosphorylation of signaling proteins involved in protein synthesis were measured at rest and after resistance exercise. RESULTS: BOLUS increased blood essential amino acid (EAA) concentrations above those of PULSE (162% compared with 53%, P < 0.001) 60 min after exercise, whereas PULSE resulted in a smaller but sustained increase in aminoacidemia that remained elevated above BOLUS amounts later (180-220 min after exercise, P < 0.05). Despite an identical net area under the EAA curve, MPS was elevated to a greater extent after BOLUS than after PULSE early (1-3 h: 95% compared with 42%) and later (3-5 h: 193% compared with 121%) (both P < 0.05). There were greater changes in the phosphorylation of the Akt-mammalian target of rapamycin pathway after BOLUS than after PULSE. CONCLUSIONS: Rapid aminoacidemia in the postexercise period enhances MPS and anabolic signaling to a greater extent than an identical amount of protein fed in small pulses that mimic a more slowly digested protein. A pronounced peak aminoacidemia after exercise enhances protein synthesis. This trial was registered at clinicaltrials.gov as NCT01319513.

Enhanced amino acid sensitivity of myofibrillar protein synthesis persists for up to 24 h after resistance exercise in young men.

We aimed to determine whether an exercise-mediated enhancement of muscle protein synthesis to feeding persisted 24 h after resistance exercise. We also determined the impact of different exercise intensities (90% or 30% maximal strength) or contraction volume (work-matched or to failure) on the response at 24 h of recovery. Fifteen men (21 ± 1 y, BMI = 24.1 ± 0.8 kg · m(-2)) received a primed, constant infusion of l-[ring-(13)C(6)]phenylalanine to measure muscle protein synthesis after protein feeding at rest (FED; 15 g whey protein) and 24 h after resistance exercise (EX-FED). Participants performed unilateral leg exercises: 1) 4 sets at 90% of maximal strength to failure (90FAIL); 2) 30% work-matched to 90FAIL (30WM); or 3) 30% to failure (30FAIL). Regardless of condition, rates of mixed muscle protein and sarcoplasmic protein synthesis were similarly stimulated at FED and EX-FED. In contrast, protein ingestion stimulated rates of myofibrillar protein synthesis above fasting rates by 0.016 ± 0.002%/h and the response was enhanced 24 h after resistance exercise, but only in the 90FAIL and 30FAIL conditions, by 0.038 ± 0.012 and 0.041 ± 0.010, respectively. Phosphorylation of protein kinase B on Ser473 was greater than FED at EX-FED only in 90FAIL, whereas phosphorylation of mammalian target of rapamycin on Ser2448 was significantly increased at EX-FED above FED only in the 30FAIL condition. Our results suggest that resistance exercise performed until failure confers a sensitizing effect on human skeletal muscle for at least 24 h that is specific to the myofibrillar protein fraction.

Carbohydrate does not augment exercise-induced protein accretion versus protein alone.

PURPOSE: We tested the thesis that CHO and protein coingestion would augment muscle protein synthesis (MPS) and inhibit muscle protein breakdown (MPB) at rest and after resistance exercise. METHODS: Nine men (age=23.0±1.9 yr, body mass index=24.2±2.1 kg·m) performed two unilateral knee extension trials (four sets×8-12 repetitions to failure) followed by consumption of 25 g of whey protein (PRO) or 25 g of whey protein plus 50 g of maltodextrin (PRO+CARB). Muscle biopsies and stable isotope methodology were used to measure MPS and MPB. RESULTS: The areas under the glucose and insulin curves were 17.5-fold (P<0.05) and 5-fold (P<0.05) greater, respectively, for PRO+CARB than for PRO. Exercise increased MPS and MPB (both P<0.05), but there were no differences between PRO and PRO+CARB in the rested or exercised legs. Phosphorylation of Akt was greater in the PRO+CARB than in the PRO trial (P<0.05); phosphorylations of Akt (P=0.05) and acetyl coA carboxylase-ß (P<0.05) were greater after exercise than at rest. The concurrent ingestion of 50 g of CHO with 25 g of protein did not stimulate mixed MPS or inhibit MPB more than 25 g of protein alone either at rest or after resistance exercise. CONCLUSIONS: Our data suggest that insulin is not additive or synergistic to rates of MPS or MPB when CHO is coingested with a dose of protein that maximally stimulates rates of MPS.

Acute {beta}-adrenergic stimulation does not alter mitochondrial protein synthesis or markers of mitochondrial biogenesis in adult men.

Exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is dramatically inhibited in mice pretreated with a beta-adrenergic receptor (beta-AR) antagonist, suggesting that beta-ARs play an important role in the regulation of skeletal muscle PGC-1alpha expression, and potentially, mitochondrial biogenesis. Accordingly, we hypothesized that acute beta-AR stimulation would induce transcriptional pathways involved in skeletal muscle mitochondrial biogenesis in humans. Whole body protein turnover (WBPT), myofibrillar protein synthesis (MyPS), skeletal muscle mitochondrial protein synthesis (MiPS), and mitochondrial biogenic signaling were determined in samples of vastus lateralis obtained on two separate occasions in 10 young adult males following 1 h of continuous intravenous administration of saline (CON) or a nonspecific beta-AR agonist [isoproterenol (ISO): 12 ng.kg fat free mass(-1).min(-1)], combined with coinfusion of [1,2](13)C-leucine. beta-AR stimulation induced appreciable increases in heart rate and systolic blood pressure (both P < 0.001) but did not affect mitochondrial biogenic signaling (no change in PGC-1alpha, TFAM, NRF-1, NRF-2, COX, or NADHox expression via RT-PCR; P > 0.05). Additionally, MiPS [CON: 0.099 +/- 0.028, ISO: 0.074 +/- 0.046 (mean +/- SD); P > 0.05] and MyPS (CON: 0.059 +/- 0.008, ISO: 0.055 +/- 0.009; P > 0.05), as well as measures of WBPT were unaffected. On the basis of this investigation, we conclude that acute intravenous beta-AR stimulation does not increase mitochondrial protein synthesis or biogenesis signals in skeletal muscle.

Differential stimulation of myofibrillar and sarcoplasmic protein synthesis with protein ingestion at rest and after resistance exercise.

We aimed to determine whether there is a differential stimulation of the contractile myofibrillar and the cellular sarcoplasmic proteins after ingestion of protein and how this is affected by resistance exercise. Fasted (FAST) muscle protein synthesis was measured in seven healthy young men with a primed constant infusion of L-[ring-(13)C(6)]phenylalanine. Participants then performed an intense bout of unilateral resistance exercise followed by the consumption of 25 g of whey protein to maximally stimulate protein synthesis. In the rested (FED) leg myofibrillar (MYO) protein synthesis was elevated (P < 0.01) above FAST at 3 h (approximately 163%) but not at 1 and 5 h (P > 0.05). In contrast, MYO protein synthesis in the exercised (FED-EX) leg was stimulated above FAST at 1, 3 and 5 h (approximately 100, 216, and 229%, respectively; P < 0.01) with the increase at 5 h being greater than FED (P < 0.01). Thus, the synthesis of muscle contractile proteins is stimulated by both feeding and resistance exercise early (1 h) but has a greater duration and amplitude after resistance exercise. Sarcoplasmic (SARC) protein synthesis was similarly elevated (P < 0.01) above FAST by approximately 104% at 3 h in both FED and FED-EX suggesting SARC protein synthesis is stimulated by feeding but that this response is not augmented by resistance exercise. In conclusion, myofibrillar and sarcoplasmic protein synthesis are similarly, but transiently, stimulated with protein feeding. In contrast, resistance exercise rapidly stimulates and sustains the synthesis of only the myofibrillar protein fraction after protein ingestion. These data highlight the importance of measuring the synthetic response of specific muscle protein fractions when examining the effects of exercise and nutrition.

Resistance exercise decreases eIF2Bepsilon phosphorylation and potentiates the feeding-induced stimulation of p70S6K1 and rpS6 in young men.

We investigated the effect of resistance exercise and feeding on the activation of signaling proteins involved in translation initiation. Nine young men (23.7+/-0.41 yr; BMI=25.5+/-1.0 kg/m2; means+/-SE) were tested twice after they performed a strenuous bout of unilateral resistance exercise, such that their contralateral leg acted as a nonexercised comparator, in either the fasted and fed [1,000 kJ, each 90 min (3 doses): 10 g protein, 41 g carbohydrate, 4 g fat] states. Muscle biopsies were obtained 6 h postexercise from both legs, resulting in four experimental conditions: rest-fasted, rest-fed, exercise-fasted, and exercise-fed. Feeding increased PKB/Akt (Ser473) phosphorylation (P<0.05), while exercise increased the phosphorylation of Akt and the downstream 70 kDa S6 protein kinase (p70S6K1, Thr389) and ribosomal protein S6 (rpS6, Ser235/236, Ser240/244; all P<0.05). The combination of resistance exercise and feeding increased the phosphorylation of p70S6K1 (Thr389) and rpS6 (Ser240/244) above exercise alone (P<0.05). Exercise also reduced phosphorylation of the catalytic epsilon subunit of eukaryotic initiation factor 2B (eIF2Bepsilon, Ser540; P<0.05). Mammalian target of rapamycin (mTOR, Ser2448), glycogen synthase kinase-3beta (GSK-3beta, Ser9), and focal adhesion kinase (FAK, Tyr576/577) phosphorylation were unaffected by either feeding or resistance exercise (all P>0.14). In summary, feeding resulted in phosphorylation of Akt, while resistance exercise stimulated phosphorylation of Akt, p70S6K1, rpS6, and dephosphorylation eIF2Bepsilon with a synergistic effect of feeding and exercise on p70(S6K1) and its downstream target rpS6. We conclude that resistance exercise potentiates the effect of feeding on the phosphorylation and presumably activation of critical proteins involved in the regulation of muscle protein synthesis in young men.

Resistance training alters the response of fed state mixed muscle protein synthesis in young men.

Ten healthy young men (21.0 +/- 1.5 yr, 1.79 +/- 0.1 m, 82.7 +/- 14.7 kg, means +/- SD) participated in 8 wk of intense unilateral resistance training (knee extension exercise) such that one leg was trained (T) and the other acted as an untrained (UT) control. After the 8 wk of unilateral training, infusions of L-[ring-d(5)]phenylalanine, L-[ring-(13)C(6)]phenylalanine, and d(3)-alpha-ketoisocaproic acid were used to measure mixed muscle protein synthesis in the T and UT legs by the direct incorporation method [fractional synthetic rate (FSR)]. Protein synthesis was determined at rest as well as 4 h and 28 h after an acute bout of resistance exercise performed at the same intensity relative to the gain in single repetition maximum before and after training. Training increased mean muscle fiber cross-sectional area only in the T leg (type I: 16 +/- 10%; type II: 20 +/- 19%, P < 0.05). Acute resistance exercise increased muscle protein FSR in both legs at 4 h (T: 162 +/- 76%; UT: 108 +/- 62%, P < 0.01 vs. rest) with the increase in the T leg being significantly higher than in the UT leg at this time (P < 0.01). At 28 h postexercise, FSR in the T leg had returned to resting levels; however, the rate of protein synthesis in the UT leg remained elevated above resting (70 +/- 49%, P < 0.01). We conclude that resistance training attenuates the protein synthetic response to acute resistance exercise, despite higher initial increases in FSR, by shortening the duration for which protein synthesis is elevated.