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This study aimed to compare the effects of an 8-week creatine (CR) or placebo (PL) supplementation on muscle strength, thickness, endurance, and body composition employing different training paradigms with blood flow restriction (BFR) vs. traditional resistance training (TRAD). Seventeen healthy males were randomized between the PL ( n = 9) and CR ( n = 8) groups. Participants were trained unilaterally utilizing a within-between subject bicep curl exercise where each arm was allocated to TRAD or BFR for 8 weeks. Muscular strength, thickness, endurance, and body composition were evaluated. Creatine supplementation promoted increases in muscle thickness in TRAD and BFR compared with their placebo counterparts, however, without a significant difference between treatments ( p = 0.349). TRAD training increased maximum strength (1 repetition maximum (1RM)) compared with BFR after 8 weeks of training ( p = 0.021). Repetitions to failure at 30% of 1RM were increased in the BFR-CR group compared with the TRAD-CR group ( p = 0.004). Repetitions to failure at 70% 1RM were increased from weeks 0–4 ( p

Lauver, JD, Moran, A, Guilkey, JP, Johnson, KE, Zanchi, NE, and Rotarius, TR. Acute responses to cycling exercise with blood flow restriction during various intensities. J Strength Cond Res XX(X): 000-000, 2021-The purpose of this study was to investigate the acute physiological responses during cycling at various intensities with blood flow restriction (BFR). Participants (N = 9; V[Combining Dot Above]O2peak = 36.09 ± 5.80 ml·kg-1·min-1) performed 5 protocols: high-intensity (HIGH), control (CON-90), 90% of ventilatory threshold (VT) work rate with BFR (90-BFR), 70% of VT with BFR (70-BFR), and 30% V[Combining Dot Above]O2peak with BFR (30-BFR). Protocols consisted of five 2-minute work intervals interspersed with 1-minute recovery intervals. Blood flow restriction pressure was 80% of limb occlusion pressure. V[Combining Dot Above]O2, muscle excitation, tissue oxygen saturation (StO2), discomfort, and level of perceived exertion (RPE) were assessed. Muscle excitation was higher during HIGH (302.9 ± 159.9 %BSL [baseline]) compared with 70-BFR (99.7 ± 76.4 %BSL) and 30-BFR (98.2 ± 70.5 %BSL). StO2 was greater during 90-BFR (40.7 ± 12.5 [INCREMENT]BSL), 70-BFR (34.4 ± 15.2 [INCREMENT]BSL), and 30-BFR (31.9 ± 18.7 [INCREMENT]BSL) compared with CON-90 (4.4 ± 11.5 [INCREMENT]BSL). 90-BFR (39.6 ± 12.0 [INCREMENT]BSL) resulted in a greater StO2-Avg compared with HIGH (20.5 ± 13.8 [INCREMENT]BSL). Also, HIGH (23.68 ± 5.31 ml·kg-1·min-1) resulted in a greater V[Combining Dot Above]O2 compared with 30-BFR (15.43 ± 3.19 ml·kg-1·min-1), 70-BFR (16.65 ± 3.26 ml·kg-1·min-1), and 90-BFR (18.28 ± 3.89 ml·kg-1·min-1); 90-BFR (intervals: 4 = 15.9 ± 2.3; intervals: 5 = 16.4 ± 2.5) resulted in a greater RPE compared with 30-BFR (intervals: 4 = 13.3 ± 1.4; intervals: 5 = 13.7 ± 1.7) during intervals 4 and 5. These results suggest that when adding BFR to various intensities of aerobic exercise, consideration should be given to peak work and VT to provide a balance between high local physiological stress and perceptual responses.

Lima-Soares, F, Pessoa, KA, Torres Cabido, CE, Lauver, J, Cholewa, J, Rossi, FE, and Zanchi, NE. Determining the arterial occlusion pressure for blood flow restriction: Pulse oximeter as a new method compared with a handheld Doppler. J Strength Cond Res 36(4): 1120-1124, 2022-In laboratorial and clinical settings, the use of Doppler ultrasound equipment has been considered the gold standard method to determine arterial occlusion pressure (AOP). However, the use of Doppler equipment is inherently limited to the technical expertise needed to perform AOP measurements. To overcome the technical difficulties of the use of Doppler equipment use in the determination of AOP, a simpler and less subjective methodology would be helpful for blood flow restriction (BFR) practitioners. In this regard, portable pulse oximetry has been largely used in clinical practice for measuring systolic pressures, as well as loss or recovery of pulse, with results similar to those observed with the use of Doppler equipment. For such purposes, the AOP from young male and female subjects was evaluated after different body positions (standing, seated, and supine positions). Loss of capillary blood flow or AOP was readily determined by simple visual inspection for the pulse oximeter and loss of sound for the Doppler equipment. The results presented herein strongly suggest the use of the portable pulse oximetry equipment as reliable, when compared with the handheld Doppler (seated k = 0.962, standing k = 0.845, and supine k = 0.963 and seated rs = 0.980, standing rs = 0.958, and supine rs = 0.955). Because AOP measurement by pulse oximetry is relatively easier to perform and financially more accessible than handheld Doppler equipment, BFR practitioners may benefit from this new methodology to measure AOP, thus determining individualized restriction pressures.

Increased blood flow via vasodilation, metabolite production, and venous pooling contribute to the hyperemia and cellular swelling experienced during resistance training. It has been suggested that these effects play a role in hypertrophic adaptations. Over the past 2 decades, sport supplement products have been marketed to promote exercise hyperemia and intracellular fluid storage, thereby enhancing hypertrophy via acute swelling of myocytes. The three main classes of supplements hypothesized to promote exercise-induced hyperemia include vasodilators, such as nitric oxide precursor supplements; anaerobic energy system ergogenic aids that increase metabolite production, such as β-alanine and creatine; and organic osmolytes, such as creatine and betaine. Previous studies indicated that these dietary supplements are able to improve muscle performance and thus enhance muscle hypertrophy; however, recent evidences also point to these three classes of supplements affecting "secondary" physiological determinants of muscle mass accretion such as vasodilation, metabolite accumulation, and muscle cellular swelling. Although we recognize that the literature is relatively scarce regarding these topics, a better comprehension and discussion of these determinants can lead to increased knowledge and might guide further research regarding the proposed mechanisms of action of the identified compounds. In this case, increased knowledge may contribute to the development of improved efficacy, new products, or direct new research to specifically investigate those secondary effects. The aim of this review was to bring into focus new perspectives associated with secondary physiological effects induced by supplementation and to determine their relevance.

Made available in DSpace on 2022-04-28T19:41:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Background: Acute capsaicinoid and capsinoid supplementation has endurance and resistance exercise benefits; however, if these short-term performance benefits translate into chronic benefits when combined with resistance training is currently unknown. This study investigated changes of chronic Capsiate supplementation on muscular adaptations, inflammatory response and performance in untrained men. Methods: Twenty untrained men were randomized to ingest 12 mg Capsiate (CAP) or placebo in a parallel, double-blind design. Body composition and performance were measured at pre-training and after 6 weeks of resistance training. An acute resistance exercise session test was performed pre and post-intervention. Blood samples were collected at rest and post-resistance exercise to analyze Tumor necrosis factor- (TNF-), Soluble TNF- receptor (sTNF-r), Interleukin-6 (IL-6) and Interleukin-10 (IL-10). Results: Exercise and CAP supplementation increased fat-free mass in comparison to baseline by 1.5 kg (P < 0.001), however, the majority of the increase (1.0 kg) resulted from an increase in total body water. The CAP change scores for fat-free mass were significantly greater in comparison to the placebo (CAP ∆%= 2.1 ± 1.8 %, PLA ∆%= 0.7 ± 1.3 %, P = 0.043) and there was a significant difference between groups in the bench press exercise (P = 0.034) with greater upper body strength change score for CAP (∆%= 13.4 ± 9.1 %) compared to placebo (∆%= 5.8 ± 5.2 %), P = 0.041. CAP had no effect on lower body strength and no supplementation interactions were observed for all cytokines in response to acute resistance exercise (P > 0.05). Conclusion: Chronic Capsiate supplementation combined with resistance training during short period (6 weeks) increased fat-free mass and upper body strength but not inflammatory response and performance in young untrained men. Immunometabolism of Skeletal Muscle and Exercise Research Group Department of Physical Education Federal University of Piauí (UFPI), “Ministro Petrônio Portella” Campus Department of Exercise Physiology University of Lynchburg Increnovo LLC, 2138 E Lafayette Pl Laboratory of Cellular and Molecular Biology of Skeletal Muscle (LABCEMME) Department of Physical Education Federal University of Maranhão Department of Nutrition University of Western São Paulo (UNOESTE) Department of Biophysics and Physiology Federal University of Piaui, Campus Minister Petrônio Portela Exercise and Immunometabolism Research Group Department of Physical Education São Paulo State University (UNESP) University São Judas Tadeu Associate Professor at Graduation Program in Science and Health Federal University of Piaui (UFPI) Exercise and Immunometabolism Research Group Department of Physical Education São Paulo State University (UNESP)

Purpose To screen for candidate hub genes associated with the effects of exercise on melanoma tumor tissues and to review the potential signaling pathways involved in this process using bioinformatics analysis. Methods The GSE62628 expression profile was downloaded from Gene Expression Omnibus database. This data set contains 10 melanoma tumor tissues from two groups of exercise and nonexercise mice. The R software was utilized to identify differentially expressed genes between samples, and functional annotation and pathway analysis were performed. Results were visualized using Cytoscape software. Results In total, 315 differentially expressed genes were obtained, including 294 upregulated and 21 downregulated genes. The functional analysis showed that these genes were mainly enriched in immune response, inflammatory response, and positive regulation of the ERK1/2 cascade in biological process functional groups. The top 10 candidate hub genes were C3, Kng1, C3ar1, Ptafr, Fgg, Alb, Pf4, Orm1, Aldh3b1, and Apob. The pathway analysis of the most significant module identified from the protein-protein interaction network revealed that the complement and coagulation cascades, Staphylococcus aureus infection, cytokine-cytokine receptor interaction, chemokine signaling pathway and phagosome were mainly involved. C3, C3ar1, Kng1, Ptafr, and Fgg may be the critical genes in the complement and coagulation cascades pathway, and S. aureus in the infection pathway. Conclusions Exercise may ameliorate the immune response and inflammatory response in melanoma tissue, and further studies exploring their relationships are warranted.

Previous research has demonstrated the positive effects of concurrent/combined aerobic and resistance exercise or leucine supplementation on skeletal muscle protein synthesis (MPS) and hypertrophy in aging organisms. However, the effects of a multimodal intervention which combines both aerobic and resistance exercise and leucine supplementation has not been fully elucidated. Eighteen month old and 2 month old C57BL/6 mice were assigned to aging control (AC, n = 8), aging and multimodal intervention (AMI, n = 8) and young control (YC, n = 8). Mice in the YC and AC groups were fed an alanine-rich diet (3.4%), and mice in the AMI group received an isonitrogenous leucine-supplemented (5%) diet in combination with combined aerobic (30 minutes swimming) and resistance exercise training (incremental jumping submersed in water with overload corresponding to 40%-50% body weight) for a total of 4 weeks. The gastrocnemius muscles were dissected for western blotting detection (signaling proteins involved in MPS) and the ex vivo determination of protein synthesis and protein content. The muscle strength of the hind limbs was measured pre-experiment and repeated once per week on Sunday for 4 weeks. Mice in the AC and AMI groups showed lower ex vivo protein synthesis, protein content, expression of signaling proteins involved in MPS, maximal grip strength but higher plasma cortisol compared with the YC group post intervention. When compared to AC mice, the multimodal treatment led to lower activity of Sestrin2, higher expression of PI3K III and the phosphorylation of mTOR, p70S6K and 4E-BP1, as well as higher plasma leucine, wet gastrocnemius muscle weight and muscle weight to body weight ratio. Furthermore, the multimodal intervention induced more pronounced anabolic response such as higher ex vivo protein synthesis rate, total protein content, and myofibrillar fractions in gastrocnemius muscle, and greater maximum grip strength. The present research shows that a multimodal intervention including combined both aerobic and resistance exercise training and 5% leucine supplementation has the potential to maintain skeletal muscle protein synthesis and attenuate losses in muscular strength during the aging process.

(1) Background: We investigated the effects of 28 days of beta-alanine (&beta, alanine) supplementation on the acute interference effect of high-intensity intermittent exercise (HIIE) on lower-body resistance exercise performance, body composition, and strength when combined with a resistance training program. (2) Methods: Twenty-two males were randomized into: &beta, alanine supplementation (6.4 g/day) or placebo (6.4 g/day maltodextrin) during 28 days. Total body water, intracellular and extracellular water, fat-free mass (FFM), and fat mass were assessed using bioelectrical impedance. Participants performed 5000-m HIIE (1:1 effort and rest ratio) followed by resistance exercise (four sets of 80% at 45&deg, leg press until muscular failure) at baseline and after 28 days. The resistance training program consisted of three sets of 10 to 12 RM with 90 s of rest, four days per week. (3) Results: For the post-HIIE leg press volume, higher values were observed post-training than pre-training, but no group x time interaction was observed. There was a non-significant trend for an interaction in the FFM change (&beta, alanine = 2.8% versus placebo = 1.0%, p = 0.072). (4) Conclusion: Twenty-eight days of &beta, alanine supplementation did not prevent acute strength loss during resistance exercise after high-intensity interval exercise, nor increase strength or hypertrophic adaptations associated with resistance training.

In general, nutritional sports ergogenics are designed to enhance energy production and/or improve body composition, promoting muscle growth and decreasing body fat. Many of the nutritional supplements and pharmacological substances have been used during resistance training without knowledge about the effects on human metabolism caused by their chronic administration. Before the usage or prescription of any ergogenic aid, it is important to consider some questions about that substance: Is it effective? Is it safe? Is it legal and ethical? In this chapter we will discuss the most widely used drugs and supplements among individuals engaged in resistance training—testosterone, growth hormone and insulin growth factor-1, creatine, beta-hydroxy beta-methylbutyrate and caffeine—focusing on their effects on strength and body composition, the safety of their usage, and the mechanisms of action.

Made available in DSpace on 2021-06-25T10:29:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 ABSTRACT: Conrado de Freitas, M, Rossi, FE, Colognesi, LA, de Oliveira, JVNS, Zanchi, NE, Lira, FS, Cholewa, JM, and Gobbo, LA. Postactivation potentiation improves acute resistance exercise performance and muscular force in trained men. J Strength Cond Res 35(5): 1357-1363, 2021-The purpose of this study was to investigate the effects of heavy back squat (90% one repetition maximum [1RM]) postactivation potentiation (PAP) on acute resistance exercise performance and force production in recreationally trained men, and to verify the relationship between maximal strength and the PAP response. Ten resistance-trained men randomly completed 4 experimental trials: (a) back squats without PAP (No-PAP), (b) back squats with PAP, (c) maximum voluntary isometric contraction (MVIC) of the quadriceps without PAP, and (d) MVIC with PAP. Back squats were performed with 4 sets at 70% of 1 RM with 2 minutes of rest interval. The number of squats repetitions performed was recorded for each set, and a total number of repetitions were calculated to analyze performance. Maximum voluntary isometric contraction was measured using electronic dynamometer, and the peak force and mean force were recorded. Blood lactate concentration was analyzed presquat and postsquat exercise. Repetitions performed in the first set was significantly (p < 0.001) greater in the PAP condition (22.00 ± 5.14) compared with No-PAP (15.50 ± 5.10), which resulted in significantly (p = 0.001) more total repetitions performed in the PAP (56.20 ± 17.3) condition compared with No-PAP (48.80 ± 14.5). Maximum voluntary isometric contraction peak was higher in PAP than in No-PAP (PAP = 765.7 ± 147.8 vs. No-PAP = 696.8 ± 131.5 N, p = 0.006). No significant correlations were observed between back squat 1RM relative to body mass and the PAP response in squat and MVIC. There were no significant differences in lactate concentration between conditions. In conclusion, PAP resulting from a heavy load prior back squat exercise improved total volume during resistance exercise. In addition, PAP was effective to increase force production during MVIC, but there was no relationship between relative 1RM values and the PAP response in trained men. Skeletal Muscle Assessment Laboratory (LABSIM) Department of Physical Education School of Technology and Sciences São Paulo State University (UNESP) Department of Physical Education School of Technology and Sciences São Paulo State University (UNESP), Post Graduation Program in Movement Sciences Department of Nutrition University of Western São Paulo (UNOESTE) Department of Physical Education Immunometabolism of Skeletal Muscle and Exercise Research Group Federal University of Piauí (UFPI) Exercise and Immunometabolism Research Group Department of Physical Education São Paulo State University (UNESP) Department of Physical Education, Laboratory of Cellular and Molecular Biology of Skeletal Muscle (LABCEMME), São Luis, Brazil; and Department of Kinesiology Coastal Carolina University Skeletal Muscle Assessment Laboratory (LABSIM) Department of Physical Education School of Technology and Sciences São Paulo State University (UNESP) Department of Physical Education School of Technology and Sciences São Paulo State University (UNESP), Post Graduation Program in Movement Sciences Exercise and Immunometabolism Research Group Department of Physical Education São Paulo State University (UNESP)

Blood flow restriction (BFR) combined with low-intensity strength training has been shown to increase skeletal muscle mass and strength in a variety of populations. BFR results in a robust metabolic stress which is hypothesized to induce muscle growth via increased recruitment of fast-twitch muscle fibers, a greater endocrine response, and/or enhancing the cellular swelling contribution to the hypertrophic process. Following exercise, neutrophils are the first immune cells to initiate the tissue remodeling process via several mechanisms including an increased production of cytokines and recruitment of monocytes/macrophages, which facilitate the phagocytosis of foreign particles, the differentiation of myoblasts, and the formation of new myotubes. Thus, the purpose of this review was to discuss the mechanisms through which metabolic stress and immune cell recruitment may induce skeletal muscle remodeling following BFR strength training.

It is commonly accepted that adequate carbohydrate availability is necessary for optimal endurance performance. However, for strength- and physique-based athletes, sports nutrition research and recommendations have focused on protein ingestion, with far less attention given to carbohydrates. Varying resistance exercise protocols, such as differences in intensity, volume, and intraset rest prescriptions between strength-training and physique-training goals elicit different metabolic responses, which may necessitate different carbohydrate needs. The results of several acute and chronic training studies suggest that although severe carbohydrate restriction may not impair strength adaptations during a resistance training program, consuming an adequate amount of carbohydrate in the days leading up to testing may enhance maximal strength and strength-endurance performance. Although several molecular studies demonstrate no additive increases in postexercise mammalian target of rapamycin 1 phosphorylation with carbohydrate and protein compared with protein ingestion alone, the effects of chronic resistance training with carbohydrate restriction on muscle hypertrophy are conflicting and require further research to determine a minimal carbohydrate threshold necessary to optimize muscle hypertrophy. This review summarizes the current knowledge regarding carbohydrate availability and resistance training outcomes and poses new research questions that will better help guide carbohydrate recommendations for strength and physique athletes. In addition, given that success in physique sports is based on subjective appearance, and not objective physical performance, we also review the effects of subchronic carbohydrate ingestion during contest preparation on aesthetic appearance.

Doxorubicin (DOX) is a chemotherapy agent widely used in clinical practice, and it is very efficient in tumor suppression, but the use of DOX is limited by a strong association with the development of severe muscle atrophy and cardiotoxicity effects. Reversion or neutralization of the muscular atrophy can lead to a better prognosis. Recent studies have proposed that the negative effect of DOX on skeletal muscle is linked to its inhibition of AMP-activated protein kinase (AMPk), a key mediator of cellular metabolism. On the basis of this, our goal was to evaluate if aerobic exercise or metformin treatment, activators of AMPk, would be able to attenuate the deleterious effects on skeletal muscle induced by the DOX treatment. C57BL6 mice received either saline (control) or DOX (2.5 mg/kg body weight) intraperitoneally, twice a week. The animals on DOX were further divided into groups that received adjuvant treatment in the form of moderate aerobic physical exercise (DOX+T) or metformin gavage (300 mg/body weight/day). Body weight, metabolism, distance run, muscle fiber cross-sectional area (CSA), and protein synthesis and degradation were assessed. We demonstrated that aerobic training, but not metformin, associated with DOX increased the maximal aerobic capacity without changing muscle mass or fiber CSA, rescuing the muscle fatigue observed with DOX treatment alone. This improvement was associated with AMPk activation, thus surpassing the negative effects of DOX on muscle performance and bioenergetics. In conclusion, aerobic exercise increases AMPk activation and improved the skeletal muscle function, reducing the side effects of DOX.

The positive influence of animal-based protein supplementation during muscle-damaging exercise has been widely studied. However, the effects of plant-based proteins remain unclear and require further clarification. This study investigated the protective role of oat protein against exercise induced muscle damage (EIMD), subsequent inflammation, and loss of performance induced by downhill running. Subjects consumed either oat protein (25 g protein) or a placebo for 14 days prior to a downhill running test and then for 4 days thereafter. Treatments with oat protein for 19 days markedly alleviated eccentric exercise induced skeletal muscle soreness, and reduced the elevation of plasma IL-6 concentrations and serum creatine kinase, myoglobin and C reactive protein contents. In addition, oat protein supplementation significantly inhibited limb edema following damaging exercise, and the adverse effects on muscle strength, knee-joint range of motion, and vertical jump performance were lessened. Furthermore, the administration of oat protein facilitated recovery from exhaustive downhill running in this study. These findings demonstrated that oat protein supplementation has the potential to alleviate the negative effects of eccentric exercise in untrained young males.

Dietary proteins/essential amino acids (EAAs) are nutrients with anabolic properties that may increase muscle mass or attenuate muscle loss during immobilization and aging via the stimulation of muscle protein synthesis (MPS). An EAA's anabolic threshold, capable to maximize the stimulation of MPS has been hypothesized, but during certain conditions associated with muscle loss, this anabolic threshold seems to increase which reduces the efficacy of dietary EAAs to stimulate MPS. Preliminary studies have demonstrated that acute ingestion of dietary proteins/EAA (with a sufficient amount of leucine) was capable to restore the postprandial MPS during bed rest, immobilization or aging; however, whether these improvements translate into chronic increases (or attenuates loss) of muscle mass is equivocal. For example, although free leucine supplementation acutely increases MPS and muscle mass in some chronic studies, other studies have reported no increases in muscle mass following chronic leucine supplementation. In contrast, chronically increasing leucine intake via the consumption of an overall increase in dietary protein appears to be the most effective dietary intervention toward increasing or attenuating lean mass during aging; however, more research investigating the optimal dose and timing of protein ingestion is necessary. Several studies have demonstrated that decreases in postprandial MPS as a result of increased circulating oxidative and inflammatory are more responsible than muscle protein breakdown for the decreases in muscle mass during disuse and health aging. Therefore, nutritional interventions that reduce oxidation or inflammation in conjunction with higher protein intakes that overcome the anabolic resistance may enhance the MPS response to feeding and either increase muscle mass or attenuate loss. In preliminary studies, antioxidant vitamins and amino acids with antioxidant or anti-inflammatory properties show potential to restore the anabolic response associated with protein ingestion. More research, however, is required to investigate if these nutrients translate to increases in MPS and, ultimately, increased lean mass in aging humans. The purpose of the present review is to discuss the role of protein/EAA intake to enhance postprandial MPS during conditions associated with muscle loss, and bring new perspectives and challenges associated nutritional interventions aimed to optimize the anabolic effects of dietary protein/EAAs ingestion.

β-Hydroxy-β-methylbutyrate (HMB) is a leucine-derived compound with anabolic and anticatabolic properties that may improve both clinical and performance outcomes. Clinically, HMB supplementation has been shown to decrease muscle proteolysis and spare muscle mass during catabolic states associated with muscle wasting syndromes. In resistance training studies, HMB may promote enhanced gains in muscle mass and strength. When evaluating the potential effects of HMB, dosage, form (calcium and the free acid form), and subject status (atrophic or anabolic states) must be taken into consideration. This chapter aims to describe general scientific evidence on HMB supplementation with regard to clinical outcomes, as well as their effects associated with resistance training and other sports. Possible mechanisms of action are also discussed in detail, based on the physiological, biochemical, and cellular/molecular literature.

Human muscle hypertrophy brought about by voluntary exercise in laboratorial conditions is the most common way to study resistance exercise training, especially because of its reliability, stimulus control and easy application to resistance training exercise sessions at fitness centers. However, because of the complexity of blood factors and organs involved, invasive data is difficult to obtain in human exercise training studies due to the integration of several organs, including adipose tissue, liver, brain and skeletal muscle. In contrast, studying skeletal muscle remodeling in animal models are easier to perform as the organs can be easily obtained after euthanasia; however, not all models of resistance training in animals displays a robust capacity to hypertrophy the desired muscle. Moreover, some models of resistance training rely on voluntary effort, which complicates the results observed when animal models are employed since voluntary capacity is something theoretically impossible to measure in rodents. With this information in mind, we will review the modalities used to simulate resistance training in animals in order to present to investigators the benefits and risks of different animal models capable to provoke skeletal muscle hypertrophy. Our second objective is to help investigators analyze and select the experimental resistance training model that best promotes the research question and desired endpoints. J. Cell. Physiol. 229: 1148–1156, 2014. © 2013 Wiley Periodicals, Inc.

Betaine is a methyl derivative of glycine first isolated from sugar beets. Betaine consumed from food sources and through dietary supplements presents similar bioavailability and is metabolized to di-methylglycine and sarcosine in the liver. The ergogenic and clinical effects of betaine have been investigated with doses ranging from 500 to 9,000 mg/day. Some studies using animal models and human subjects suggest that betaine supplementation could promote adiposity reductions and/or lean mass gains. Moreover, previous investigations report positive effects of betaine on sports performance in both endurance- and resistance-type exercise, despite some conflicting results. The mechanisms underlying these effects are poorly understood, but could involve the stimulation of lipolysis and inhibition of lipogenesis via gene expression and subsequent activity of lipolytic-/lipogenic-related proteins, stimulation of autocrine/endocrine IGF-1 release and insulin receptor signaling pathways, stimulation of growth hormone secretion, increased creatine synthesis, increases in protein synthesis via intracellular hyper-hydration, as well as exerting psychological effects such as attenuating sensations of fatigue. However, the exact mechanisms behind betaine action and the long-term effects of supplementation on humans remain to be elucidated. This review aims to describe evidence for the use of betaine as an ergogenic and esthetic aid, and discuss the potential mechanisms underlying these effects.

Objectives: The purpose of this study was to investigate the effects of intensity on rating of perceived exertion (RPE) during multiple sets to volitional failure in bench press exercise. Design and Methods: Thirteen moderately resistance trained men performed 2 experimental sessions in random order: 3 sets to failure in bench press with 1 minute rest at an intensity of 50% and 70% of 1 repetition maximum (1RM). RPE was measured using the OMNI scale after each set. Readiness to Invest in Physical (RTIPE) and Mental (RTIME) Effort were assessed before each set. Results: Repetitions to failure (46.46 ± 9.43 vs 26.62 ± 8.19; P

Branched-chain amino acids (BCAA) (especially leucine) have been shown to activate protein synthesis pathways, decrease proteolysis and increase insulin sensitivity. Furthermore, it appears that leucine can be used as a nutritional therapy to avoid sarcopenia and skeletal muscle atrophy due to immobilization or glucocorticoid treatment. However, it is of note that all of these conditions are related to insulin resistance to varying degrees and affect different tissues, particularly skeletal muscle. Additionally, evidence from recent studies demonstrate that a combination of protein containing high levels of leucine with nutrients containing saturated fatty acids or an excess of leucine are capable of inducing insulin resistance. From this discussion, a few major questions arise. First, what is the role of a combination of macronutrients in inducing insulin resistance? Second, in insulin resistance, does leucine supplementation follow the same path observed under healthy conditions? Finally, what are the dose-dependent outcome and the latency of leucine effect under such conditions? The present article discusses these questions based on data from the literature and experiments performed by our group.

Several studies have indicated a positive influence of leucine supplementation and aerobic training on the aging skeletal muscle signaling pathways that control muscle protein balance and muscle remodeling. However, the effect of a combined intervention requires further clarification. Thirteen month old CD-1(®) mice were subjected to moderate aerobic exercise (45 min swimming per day with 3% body weight workload) and fed a chow diet with 5% leucine or 3.4% alanine for 8 weeks. Serum and plasma were prepared for glucose, urea nitrogen, insulin and amino acid profile analysis. The white gastrocnemius muscles were used for determination of muscle size and signaling proteins involved in protein synthesis and degradation. The results show that both 8 weeks of leucine supplementation and aerobic training elevated the activity of mTOR (mammalian target of rapamycin) and its downstream target p70S6K and 4E-BP1, inhibited the ubiquitin-proteasome system, and increased fiber cross-sectional area (CSA) in white gastrocnemius muscle. Moreover, leucine supplementation in combination with exercise demonstrated more significant effects, such as greater CSA, protein content and altered phosphorylation (suggestive of increased activity) of protein synthesis signaling proteins, in addition to lower expression of proteins involved in protein degradation compared to leucine or exercise alone. The current study shows moderate aerobic training combined with 5% leucine supplementation has the potential to increase muscle size in fast-twitch skeletal muscle during aging, potentially through increased protein synthesis and decreased protein breakdown.

A dexametasona (DEXA) é um potente agente imunossupressor e antiinflamatório, mas apresenta importantes efeitos colaterais, tais como a atrofia muscular e a resistência à ação da insulina nos músculos esqueléticos. Neste contexto, a suplementação com leucina poderia representar uma estratégia nutricional terapêutica capaz de limitar os efeitos colaterais do tratamento com DEXA. Neste estudo, foram investigados os efeitos da suplementação com leucina em baixas e altas doses sobre a massa muscular, força muscular, assim como vários marcadores metabólicos que estão sob controle da insulina em ratos com restrição calórica e em ratos tratados com DEXA. Como a resposta da suplementação com leucina pode também estar ligada à forma de administração desse aminoácido, realizamos experimentos com leucina administradas via gavagem (bolus) versus leucina diluída no bebedouro dos animais. A suplementação com leucina demonstrou preservar a massa muscular, a força muscular voluntária média e a homeostasia da glicose em animais sob restrição calórica, mas este efeito foi observado apenas com a leucina suplementada em baixas concentrações/doses. Este efeito da leucina sobre a massa muscular esteve associado com a expressão de genes envolvidos no remodelamento da musculatura esquelética. Quanto ao efeito da leucina sobre a homeostasia da glicose, um efeito benéfico do aminoácido foi observado com a suplementação em baixas doses, o qual foi evidenciado pelos dados metabólicos avaliados. No entanto, sob tratamento com DEXA, a suplementação com leucina agravou o estado \"diabetogênico\" dos animais. Por último, a via de administração da leucina influenciou significativamente a resposta a este aminoácido, onde a suplementação via gavagem mostrou-se menos prejudicial do que a suplementação com leucina diluída nos bebedouros, ao menos em relação ao aspecto diabetogênico causado pelo tratamento concomitante com DEXA Dexamethasone (DEXA) is a potent immunosupressor and anti-inflammatory agent but presents side effects such as muscle atrophy and insulin resistance in skeletal muscles. In this context, leucine supplementation may represent a way to limit the DEXA side effects. In this study, we investigated the effects of a low and a high dose of leucine on muscle mass, on muscle strength as well as on several metabolic markers that are under insulin control in energy-restricted and DEXA-treated rats. Since leucine response may also be linked to the way of administration of this amino acid, we performed experiments with leucine given in a gavage versus leucine given in drinking water way. Leucine supplementation was found to spare muscle mass, voluntary medium strength and glucose homeostasis in energy restricted animals but the effect was observed only with the low dose/concentration of leucine. The leucine effect on muscle mass was associated with expression of genes involved in muscle remodeling. However, under DEXA treatment, leucine supplementation was found to aggravate the diabetogenic state. Lastly, the route of leucine administration was found to significantly influence this variable to this amino acid, where leucine supplemented via gavage demonstrated to be less deleterious than supplemented diluted in the water drink, concomitantly with DEXA treatment

The reduction of skeletal muscle loss in pathological states, such as muscle disuse, has considerable effects in terms of rehabilitation and quality of life. Since there is no currently effective and safe treatment available for skeletal muscle atrophy, the search for new alternatives is necessary. Resistance exercise (RE) seems to be an important tool in the treatment of disuse-induced skeletal muscle atrophy by promoting positive functional (strength and power) and structural (hypertrophy and phenotypic changes) adaptive responses. Human and animal studies using different types of resistance exercise (flywheel, vascular occlusion, dynamic, isometric, and eccentric) have obtained results of great importance. However, since RE is a complex phenomenon, lack of strict control of its variables (volume, frequency, intensity, muscle action, rest intervals) limits the interpretation of the impact of the manipulation on skeletal muscle remodeling and function under disuse. The aim of this review is to critically describe the functional and morphological role of resistance exercise in disuse-induced skeletal muscle atrophy with emphasis on the principles of training.

Eur J Clin Invest 2010; 40 (8): 759–765 Abstract Background This study examined the effects of acute supramaximal exercise (∼115% VO2max) on the blood lipid profile for three different carbohydrate (CHO) storage levels (control, low and high). Methods Six male subjects were randomly divided into three different groups: control, low CHO and high CHO. These groups differed in the diet to which the subjects were submitted before each exercise session. The lipid profile [triglycerides (TG), very low-density lipoprotein (VLDL), high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, TG/HDL-C ratio and total cholesterol) was determined at rest, immediately after exercise and 1 h after exercise bouts. Results The time to exhaustion was lower in the low CHO condition compared with the control and high CHO condition (3·59 ± 0·72; 2·91 ± 0·56; and 4·26 ± 0·69 min; P 0·05). Conclusions These results indicate that a supramaximal exercise session has no significant effects on lipid metabolism.

Glucocorticoid hormones are important regulators of several physiological processes. Despite having been initially named based on their role in glucose metabolism, glucocorticoids are also fundamental in the regulation of developmental, metabolic, and neurobiological processes, as well as several other biological functions. Due to their involvement in a diverse array of biological pathways, its wide spectrum of action, it is predicted that a wide range of genes may have their expression regulated by the activated glucocorticoid receptor (GR). In fact, it has been demonstrated that in addition to the regulation of several effectors genes, the expression of the gene encoding for GR itself is regulated by physiological stimuli and fine-tuning mechanisms. Importantly, such generalized effector responses and fine-tuning responses seem to be largely mediated by mechanisms of gene regulation. Therefore, this review aims to describe the mechanisms of gene regulation by glucocorticoid hormones, which are capable of regulating differential gene transcription, within a physiological context. From this discussion, we hope to shed light on how a single molecule that is capable of exerting such divergent effects is also capable of promoting such distinct responses in different target tissues.

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin 6 (IL-6), a cytokine that exerts inhibitory effects on several pro-inflammatory cytokines. Although dynamic chronic resistance training has been shown to produce the known "repeated bout effect", which abolishes the acute muscle damage, performing of high-intensity resistance training has been regarded highly advisable, at least from the hypertrophy perspective. On the other hand, a more therapeutic, "non-damaging" resistance training program, mainly composed of concentric forces, low frequency/low volume of training, and the same exercise, could theoretically benefit the muscle when the main issue is to avoid muscle inflammation (as in the treatment of several "low-grade" inflammatory diseases) because the acute effect of each resistance exercise session could be diminished/avoided, at the same time that the muscle is still being overloaded in a concentric manner. However, the benefits of such "less demanding" resistance training schedule on the muscle inflammatory profile have never been investigated. Therefore, we assessed the protein expression of IL-6, TNF-alpha, IL-10, IL-10/TNF-alpha ratio, and HSP70 levels and mRNA expression of SCF(beta-TrCP), IL-15, and TLR-4 in the skeletal muscle of rats submitted to resistance training. Briefly, animals were randomly assigned to either a control group (S, n = 8) or a resistance-trained group (T, n = 7). Trained rats were exercised over a duration of 12 weeks (two times per day, two times per week). Detection of IL-6, TNF-alpha, IL-10, and HSP70 protein expression was carried out by western blotting and SCF(beta-TrCP) (SKP Cullin F-Box Protein Ligases), a class of enzymes involved in the ubiquitination of protein substrates to proteasomal degradation, IL-15, and TLR-4 by RT-PCR. Our results show a decreased expression of TNF-alpha and TLR4 mRNA (40 and 60%, respectively; p0.05) in the plantar muscle from trained, when compared with control rats. In conclusion, exercise training induced decreased TNF-alpha and TLR-4 expressions, resulting in a modified IL-10/TNF-alpha ratio in the skeletal muscle. These data show that, in healthy rats, 12-week resistance training, predominantly composed of concentric stimuli and low frequency/low volume schedule, down regulates skeletal muscle production of cytokines involved in the onset, maintenance, and regulation of inflammation.

Volitional animal resistance training constitutes an important approach to modeling human resistance training. However, the lack of standardization protocol poses a frequent impediment to the production of skeletal muscle hypertrophy and the study of related physiological variables (i.e., cellular damage/inflammation or metabolic stress). Therefore, the purposes of the present study were: (1) to test whether a longterm and low frequency experimental resistance training program is capable of producing absolute increases in muscle mass; (2) to examine whether cellular damage/inflammation or metabolic stress is involved in the process of hypertrophy. In order to test this hypothesis, animals were assigned to a sedentary control (C, n ¼ 8) or a resistance trained group (RT, n ¼ 7). Trained rats performed 2 exercise sessions per week (16 repetitions per day) during 12 weeks. Our results demonstrated that the resistance training strategy employed was capable of producing absolute mass gain in both soleus and plantaris muscles (12%, p < 0.05). Furthermore, muscle tumor necrosis factor (TNF-a) protein expression (soleus muscle) was reduced by 24% ( p < 0.01) in trained group when compared to sedentary one. Finally, serum creatine kinase (CK) activity and serum lactate concentrations were not affected in either group. Such information may have practical applications if reproduced in situations where skeletal muscle hypertrophy is desired but high mechanical stimuli of skeletal muscle and inflammation are not. Copyright # 2010 John Wiley & Sons, Ltd.

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin-6 (IL-6). Acute physical exercise is known to induce a pro-inflammatory cytokine profile in the plasma. However, the effect of chronic physical exercise in the production of pro- and anti-inflammatory cytokines by the skeletal muscle has never been examined. We assessed IL-6, TNF-α, IL-1β and IL-10 levels in the skeletal muscle of rats submitted to endurance training. Animals were randomly assigned to either a sedentary group (S, n = 7) or an endurance exercise trained group (T, n = 8). Trained rats ran on a treadmill for 5 days week−1 for 8 weeks (60% VO2max). Detection of IL-6, TNF-α, IL-1β and IL-10 protein expression was carried out by ELISA. We found decreased expression of IL-1β, IL-6, TNF-α and IL-10 (28%, 27%, 32% and 37%, respectively, p

The skeletal muscle is a tissue with adaptive properties which are essential to the survival of many species. When mechanically stimulated it is liable to undergo remodeling, namely, changes in its mass/volume resulting mainly from myofibrillar protein accumulation. The mTOR pathway (mammalian target of rapamycin) via its effector p70s6k (ribosomal protein kinase S6) has been reported to be of importance to the control of skeletal muscle mass, particularly under mechanical stimulation. However, not all mechanical stimuli are capable of activating this pathway, and among those who are, there are differences in the activation magnitude. Likewise, not all skeletal muscle fibers respond to the same extent to mechanical stimulation. Such evidences suggest specific mechanical stimuli through appropriate cellular signaling to be responsible for the final physiological response, namely, the accumulation of myofibrillar protein. Lately, after the mTOR signaling pathway has been acknowledged as of importance for remodeling, the interest for the mechanical/chemical mediators capable of activating it has increased. Apart from the already known MGF (mechano growth factor), some other mediators such as phosphatidic acid (PA) have been identified. This review article comprises and discusses relevant information on the mechano-chemical transduction of the pathway mTOR, with especial emphasis on the muscle protein synthesis.

Metabolic stress is a physiological process that occurs during exercise in response to low energy that leads to metabolite accumulation [lactate, phosphate inorganic (Pi) and ions of hydrogen (H+)] in muscle cells. Traditional exercise protocol (i.e., Resistance training) has an important impact on the increase of metabolite accumulation, which influences hormonal release, hypoxia, reactive oxygen species (ROS) production and cell swelling. Changes in acute exercise routines, such as intensity, volume and rest between sets, are determinants for the magnitude of metabolic stress, furthermore, different types of training, such as low-intensity resistance training plus blood flow restriction and high intensity interval training, could be used to maximize metabolic stress during exercise. Thus, the objective of this review is to describe practical applications that induce metabolic stress and the potential effects of metabolic stress to increase systemic hormonal release, hypoxia, ROS production, cell swelling and muscle adaptations.

Human muscle hypertrophy brought about by voluntary exercise in laboratorial conditions is the most common way to study resistance exercise training, especially because of its reliability, stimulus control and easy application to resistance training exercise sessions at fitness centers. However, because of the complexity of blood factors and organs involved, invasive data is difficult to obtain in human exercise training studies due to the integration of several organs, including adipose tissue, liver, brain and skeletal muscle. In contrast, studying skeletal muscle remodeling in animal models are easier to perform as the organs can be easily obtained after euthanasia; however, not all models of resistance training in animals displays a robust capacity to hypertrophy the desired muscle. Moreover, some models of resistance training rely on voluntary effort, which complicates the results observed when animal models are employed since voluntary capacity is something theoretically impossible to measure in rodents. With this information in mind, we will review the modalities used to simulate resistance training in animals in order to present to investigators the benefits and risks of different animal models capable to provoke skeletal muscle hypertrophy. Our second objective is to help investigators analyze and select the experimental resistance training model that best promotes the research question and desired endpoints.

Resistance training is a potent stimulus to increase skeletal muscle mass. The muscle protein accretion process depends on a robust synergistic action between protein intake and overload. The intake of protein after resistance training increases plasma amino acids, which results in the activation of signaling molecules leading to increased muscle protein synthesis (MPS) and muscle hypertrophy. Although both essential and non-essential amino acids are necessary for hypertrophy, the intake of free L-leucine or high-leucine whole proteins has been specifically shown to increase the initiation of translation that is essential for elevated MPS. The literature supports the use of protein intake following resistance-training sessions to enhance MPS; however, less understood are the effects of different protein sources and timing protocols on MPS. The sum of the adaptions from each individual training session is essential to muscle hypertrophy, and thus highlights the importance of an optimal supplementation protocol. The aim of this review is to present recent findings reported in the literature and to discuss the practical application of these results. In that light, new speculations and questions will arise that may direct future investigations. The information and recommendations generated in this review should be of benefit to clinical dietitians as well as those engaged in sports.

In general, nutritional sports ergogenics are designed to enhance energy production and/or improve body composition, promoting muscle growth and decreasing body fat. Many nutritional supplements and pharmacological substances have been used during resistance training without knowledge of the effects on human metabolism caused by their chronic administration. Before the utilization or prescription of any ergogenic aid, it is important to consider some questions about that substance: Is it effective? Is it safe? Is it legal and ethical? In this chapter we discuss the most widely utilized drugs and supplements among individuals engaged in resistance training—testosterone, creatine, beta-hydroxy beta-methylbutyrate (HMB) and caffeine—focusing on their effects on strength and body composition, the safety of their utilization, and their mechanisms of action.

We examined the capacity of high-intensity intermittent training (HI-IT) to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT) system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g) were randomly distributed into 3 groups: sedentary (Sed, N = 5), HI-IT (N = 10), and moderate-intensity continuous training (MI-CT, N = 10). The trained groups were exercised for 8 weeks with a 10% (HI-IT) and a 5% (MI-CT) overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01), as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01) and lipoprotein lipase (LPL; P < 0.05). Lactate dehydrogenase also presented a higher maximal activity (nmol·min -1 ·mg protein ) in HI-IT (around 83%). We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a “time-efficient” strategy inducing metabolic adaptation. Key words: High-intensity intermittent training; Lipid metabolism; Carnitine palmitoyl transferase

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective: We aimed to evaluate the effects of resistance exercise (RE) and leucine (LEU) supplementation on dexamethasone (DEXA)-induced muscle atrophy and insulin resistance.Methods: Male Wistar rats were randomly divided into DEXA(DEX), DEXA + RE (DEX-RE), DEXA + LEU (DEX-LEU), and DEXA + RE + LEU (DEX-RE-LEU) groups. Each group received DEXA 5 mg . kg(-1) . d(-1) for 7 d from drinking water and were pair-fed to the DEX group; LEU-supplemented groups received 0.135 g . kg(-1) . d(-1) through gavage for 7 d; the RE protocol was based on three sessions of squat-type exercise composed by three sets of 10 repetitions at 70% of maximal voluntary strength capacity.Results: the plantaris mass was significantly greater in both trained groups compared with the non-trained groups. Muscle cross-sectional area and fiber areas did not differ between groups. Both trained groups displayed significant increases in the number of intermediated fibers (IIa/IIx), a decreased number of fast-twitch fibers (IIb), an increased ratio of the proteins phospho(Ser2448)/ total mammalian target of rapamycin and phospho(Thr389)/total 70-kDa ribosomal protein S6 kinase. and a decreased ratio of phospho(Ser253)/total Forkhead box protein-3a. Plasma glucose was significantly increased in the DEX-LEU group compared with the DEX group and RE significantly decreased hyperglycemia. the DEX-LEU group displayed decreased glucose transporter-4 translocation compared with the DEX group and RE restored this response. LEU supplementation worsened insulin sensitivity and did not attenuate muscle wasting in rats treated with DEXA. Conversely, RE modulated glucose homeostasis and fiber type transition in the plantaris muscle.Conclusion: Resistance exercise but not LEU supplementation promoted fiber type transition and improved glucose homeostasis in DEXA-treated rats. (C) 2012 Elsevier Inc. All rights reserved. Univ São Paulo, Lab Appl Nutr & Metab, Sch Phys Educ & Sports, São Paulo, Brazil Univ São Paulo, Inst Biomed Sci, São Paulo, Brazil Univ São Paulo, Lab Mol & Cellular Physiol Exercise, Sch Phys Educ & Sports, São Paulo, Brazil Univ São Paulo, Sch Med, Lab Expt Hypertens, São Paulo, Brazil Universidade Federal de São Paulo, Dept Biosci, São Paulo, Brazil Clermont Univ, UFR Med, UMR Nutr Humaine 1019, Clermont Ferrand, France INRA, UMR Unite Nutr Humaine 1019, F-63122 St Genes Champanelle, France Universidade Federal de São Paulo, Dept Biosci, São Paulo, Brazil FAPESP: 08/51090-1 FAPESP: 10/07062-3 FAPESP: 10/10852-6 FAPESP: 11/04690-6 Web of Science