Untrained State Research Articles

Impacts of circulating microRNAs in exercise-induced vascular remodeling.

Cardiovascular adaptation underlies all athletic training modalities, with a variety of factors contributing to overall response during exercise-induced stimulation. In this regard the role of circulating biomarkers is a well-established and invaluable tool for monitoring cardiovascular function. Specifically, novel biomarkers such as circulating cell free DNA and RNA are now becoming attractive tools for monitoring cardiovascular function with the advent of next generation technologies that can provide unprecedented precision and resolution of these molecular signatures, paving the way for novel diagnostic and prognostic avenues to better understand physiological remodeling that occurs in trained versus untrained states. In particular, microRNAs are a species of regulatory RNAs with pleiotropic effects on multiple pathways in tissue-specific manners. Furthermore, the identification of cell free microRNAs within peripheral circulation represents a distal signaling mechanism that is just beginning to be explored via a diversity of molecular and bioinformatic approaches. This article provides an overview of the emerging field of sports/performance genomics with a focus on the role of microRNAs as novel functional diagnostic and prognostic tools, and discusses present knowledge in the context of athletic vascular remodeling. This review concludes with current advantages and limitations, touching upon future directions and implications for applying contemporary systems biology knowledge of exercise-induced physiology to better understand how disruption can lead to pathology.

Mechanism of the Effect of High-Intensity Training on Urinary Metabolism in Female Water Polo Players Based on UHPLC-MS Non-Targeted Metabolomics Technique.

Objective: To study the changes in urine metabolism in female water polo players before and after high-intensity training by using ultra-high performance liquid chromatography-mass spectrometry, and to explore the biometabolic characteristics of urine after training and competition. Methods: Twelve young female water polo players (except goalkeepers) from Shanxi Province were selected. A 4-week formal training was started after 1 week of acclimatization according to experimental requirements. Urine samples (5 mL) were collected before formal training, early morning after 4 weeks of training, and immediately after 4 weeks of training matches, and labeled as T1, T2, and T3, respectively. The samples were tested by LC-MS after pre-treatment. XCMS, SIMCA-P 14.1, and SPSS16.0 were used to process the data and identify differential metabolites. Results: On comparing the immediate post-competition period with the pre-training period (T3 vs. T1), 24 differential metabolites involved in 16 metabolic pathways were identified, among which niacin and niacinamide metabolism and purine metabolism were potential post-competition urinary metabolic pathways in the untrained state of the athletes. On comparing the immediate post-competition period with the post-training period (T3 vs. T2), 10 metabolites involved in three metabolic pathways were identified, among which niacin and niacinamide metabolism was a potential target urinary metabolic pathway for the athletes after training. Niacinamide, 1-methylnicotinamide, 2-pyridone, L-Gln, AMP, and Hx were involved in two metabolic pathways before and after the training. Conclusion: Differential changes in urine after water polo games are due to changes in the metabolic pathways of niacin and niacinamide.

Elevated peak systolic blood pressure in endurance-trained athletes: Physiology or pathology?

Blood pressure is a function of cardiac output and peripheral vascular resistance. During graded exercise testing (GXT), systolic blood pressure (SBP) is expected to increase gradually along with work rate, oxygen consumption, heart rate, and cardiac output. Individuals exposed to chronic endurance training attain a greater exercise SBP than in their untrained state and sedentary counterparts, but it is currently unknown what is considered a safe upper limit. This review discusses key studies examining blood pressure response in sedentary individuals and athletes. We highlight the physiological characteristics of highly fit individuals in terms of cardiovascular physiology and exercise blood pressure and review the state of the current literature regarding the safety of high SBP during exercise in this particular subgroup. Findings from this review indicate that a consensus on what is a normal SBP response to exercise in highly fit subjects and direct causation linking high GXT SBP to pathology is lacking. Consequently, applying GXT SBP guidelines developed for a "normal" population to endurance-trained individuals appears unsupported at this time. Lack of evidence for poor outcomes leads us to infer that elevated peak SBP in this subgroup could more likely reflect an adaptive response to training, rather than a pathological outcome. Future studies should track clinical outcomes of those achieving elevated SBP and develop athlete-specific guidelines.

A hybrid fine-tuned VMD and CNN scheme for untrained compound fault diagnosis of rotating machinery with unequal-severity faults

In the case of a compound fault diagnosis of rotating machinery, when two failures with unequal severity occur in distinct parts of the system, the detection of a minor fault is a complicated and challenging task. In this case, the minor fault is overshadowed by the more severe one, and the characteristics of the compound fault are prone to the more severe one. Generally, the proposed methods in the literature consider compound failure as an individual fault type and unrelated to the corresponding single faults, either at the different locations of a sensitive component or in two separate parts, such as the bearing and gear, with approximately the same fault severity. Considering these issues, this study proposes a novel end-to-end fault diagnosis method based on fine-tuned VMD and convolutional neural network (CNN). The main idea is that CNN is trained only on a healthy and single fault dataset, without the use of compound fault data in training. In the test stage of the CNN model, the intelligent method alarms an untrained compound fault state if acquired probabilities of CNN output satisfy a set of probabilistic conditions. The performance of the fine-tuned VMD and the proposed hybrid method is evaluated by the decomposition of a simulated vibration signal and the analysis of a gearbox system with a compound fault scenario in such a way that one fault is minor and the other severe. The results obtained show the high accuracy of the proposed method in compound fault diagnosis and the feature extraction and classification of a minor fault in the presence of a more severe one.

Neural network constitutive model for crystal structures

Neural network constitutive models (NNCMs) for crystal structures are proposed based on computationally generated high-fidelity data. Stress, and tangent modulus data are generated under various strain states using empirical potentials and first-principles calculations. Strain–stress artificial neural network and strain-tangent modulus ANN are constructed. The symmetry conditions are considered for cubic, tetragonal, and hexagonal structures. The NNCMs of six face-centered cubic materials (Cu, Ni, Pd, Pt, Ag, and Au), two diamond cubic materials (Si, Ge), two tetragonal crystal materials (TiO2, ZnO), and two hexagonal crystal materials (ZnO, GaN) are constructed and tested under the untrained strain state. In particular, the performance of NNCM for cubic structure is better compared with that of the classical model. The suggested NNCM can be embedded into a nonlinear finite element method, and numerical examples are performed to verify the proposed NNCM.

PHITE: Precision High Intensity Training Through Epigenetics

PURPOSE: To investigate and mechanistically link acute molecular changes in the mRNA transcriptome and splice variant profile, miRNA profile, DNA methylome, and histone acetylation profile to changes in performance from exercise training. PHITE will: (1) Reveal potential molecular mechanisms underlying training and detraining adaptations; (2) Differentiate molecular responses to moderate vs. high intensity training, and identify potential underpinnings of inter-individual response heterogeneity; (3) Perform a rigorous proof-of-concept epigenomic biomarker study that scales to and improves Navy physical training. METHODS: This is an ongoing single-blind randomized trial of 18-27 y/o untrained adults. Participants are randomized to moderate or high intensity combined training 3 d/wk x 12 wk, followed by a 4-wk detraining period. Participants perform an acute exercise bout at wks 0 and 12 to assess acute molecular responses to exercise in untrained and trained states with serial biospecimen (muscle, blood) collections; repeated after 4 wk of detraining. Performance/phenotyping at wks 0 and 12 include aerobic power (VO2peak), strength, anaerobic power, explosive power, body composition (DXA), and phenotyping of blood and muscle. Because the trial is ongoing, randomized assignment remains blinded as groups A and B. Blinded phenotyping data were analyzed using repeated measures ANOVA for the effects of time (T), dose (A vs. B) and dose x time interaction. RESULTS: Phenotyping data on the first 51 completed participants confirm significant training effects and early indices of differential adaptations by exercise dose, along with substantial inter-individual response heterogeneity. Differential molecular mapping responses demonstrate sensitivity to exercise dose (A vs. B), timing of sample collection post-exercise, and training state (untrained vs trained vs detrained). CONCLUSION: Molecular response patterns to dose A vs. dose B share limited commonality, and differential responses across individuals provide novel preliminary evidence that dose-specific and individual-specific molecular response patterns may enable discrimination of adaptability.

Harmonic Loads Classification by Means of Currents’ Physical Components

Electric load identification and classification for smart grid environment can improve the power service for both consumers and producers. The main concept of electric load identification and classification is to disaggregate various loads and categorize them. In this paper, a new practical method for electric load identification and classification is presented. The method is based on using a power monitor to analyze a real measured current waveform of a grid-connected device. A set number of features is extracted using the currents’ physical components-based power theory decomposition. Using currents’ physical components ensures a constant number of features, which maintains the signal’s characteristics regardless of the harmonic content. These features are used to train a supervised classifier based on two techniques: artificial neural network and nearest neighbor search. The theory is outlined, and experimental results are shown. This paper demonstrates high accuracy performance in identifying an electric load from a designated database. Furthermore, the results show a definite classification of an untrained operation state of a device to the closest trained operation state, for example, the excitation angle of a dimmer. In a comparative study, the method is shown to outperform other state-of-the-art techniques, which are based on harmonic components.

Native Whey Induces Similar Adaptation to Strength Training as Milk, despite Higher Levels of Leucine, in Elderly Individuals.

Background: Large amounts of protein (40 g) or supplementing suboptimal servings of protein with leucine are able to overcome the anabolic resistance in elderly muscle. Our aim was to compare the effects of supplementation of native whey, high in leucine, with milk on gains in muscle mass and strength during a period of strength training, in elderly individuals. Methods: In this double-blinded, randomized, controlled study, a total of 30 healthy men and women received two daily servings of 20 g of either milk protein or native whey, during an 11-week strength training intervention. Muscle strength, lean mass, m. vastus lateralis thickness, muscle fiber area, and resting and post-exercise phosphorylation of p70S6K, 4E-BP1, and eEF-2 were assessed prior to and after the intervention period. Results: Muscle mass and strength increased, by all measures applied in both groups (p < 0.001), with no differences between groups (p > 0.25). p70S6K phosphorylation increased (~1000%, p < 0.045) 2 h after exercise in the untrained and trained state, with no differences between supplements. Total and phosphorylated mTORC-1 decreased after training. Conclusion: Supplementation with milk or native whey during an 11-week strength training period increased muscle mass and strength similarly in healthy elderly individuals.

Three weeks of sprint interval training improved high-intensity cycling performance and limited ryanodine receptor modifications in recreationally active human subjects.

Mechanisms underlying the efficacy of sprint interval training (SIT) remain to be understood. We previously reported that an acute bout of SIT disrupts the integrity of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor 1 (RyR1), in recreationally active human subjects. We here hypothesize that in addition to improving the exercise performance of recreationally active humans, a period of repeated SIT sessions would make the RyR1 protein less vulnerable and accelerate recovery of contractile function after a SIT session. Eight recreationally active males participated in a 3-week SIT program consisting of nine sessions of four-six 30-s all-out cycling bouts with 4min of rest between bouts. Total work performed during a SIT session and maximal power (Wmax) reached during an incremental cycling test were both increased by ~ 7.5% at the end of the training period (P < 0.05). Western blots performed on vastus lateralis muscle biopsies taken before, 1h, 24h and 72h after SIT sessions in the untrained and trained state showed some protection against SIT-induced reduction of full-length RyR1 protein expression in the trained state. SIT-induced knee extensor force deficits were similar in the untrained and trained states, with a major reduction in voluntary and electrically evoked forces immediately and 1h after SIT (P < 0.05), and recovery after 24h. Three weeks of SIT improves exercise performance and provides some protection against RyR1 modification, whereas it does not accelerate recovery of contractile function.

Integrated Myofibrillar Protein Synthesis in Recovery From Unaccustomed and Accustomed Resistance Exercise With and Without Multi-ingredient Supplementation in Overweight Older Men.

Background: We previously showed that daily consumption of a multi-ingredient nutritional supplement increased lean mass in older men, but did not enhance lean tissue gains during a high-intensity interval training (HIIT) plus resistance exercise training (RET) program. Here, we aimed to determine whether these divergent observations aligned with the myofibrillar protein synthesis (MyoPS) response to acute unaccustomed and accustomed resistance exercise.Methods: A sub-sample of our participants were randomly allocated (n = 15; age: 72 ± 7 years; BMI: 26.9 ± 3.1 kg/m2 [mean ± SD]) to ingest an experimental supplement (SUPP, n = 8: containing whey protein, creatine, vitamin D, and n-3 PUFA) or control beverage (CON, n = 7: 22 g maltodextrin) twice per day for 21 weeks. After 7 weeks of consuming the beverage alone (Phase 1: SUPP/CON only), subjects completed 12 weeks of RET (twice per week) + HIIT (once per week) (Phase 2: SUPP/CON + EX). Orally administered deuterated water was used to measure integrated rates of MyoPS over 48 h following a single session of resistance exercise pre- (unaccustomed) and post-training (accustomed).Results: Following an acute bout of accustomed resistance exercise, 0–24 h MyoPS was 30% higher than rest in the SUPP group (effect size: 0.86); however, in the CON group, 0–24 h MyoPS was 0% higher than rest (effect size: 0.04). Nonetheless, no within or between group changes in MyoPS were statistically significant. When collapsed across group, rates of MyoPS in recovery from acute unaccustomed resistance exercise were positively correlated with training-induced gains in whole body lean mass (r = 0.63, p = 0.01).Conclusion: There were no significant between-group differences in MyoPS pre- or post-training. Integrated rates of MyoPS post-acute exercise in the untrained state were positively correlated with training-induced gains in whole body lean mass. Our finding that supplementation did not alter 0–48 h MyoPS following 12 weeks of training suggests a possible adaptive response to longer-term increased protein intake and warrants further investigation. This study was registered at ClinicalTrials.gov.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02281331

Adaptation of myocardial twist in the remodelled athlete's heart is not related to cardiac output

What is the central question of this study? What is the role of heart muscle function in the increased output of remodelled, larger hearts? What is the main finding and its importance? The greater stroke volume of endurance athletes is not associated with enhanced function of the heart muscle (i.e. left ventricular twist, torsion and twist-to-shortening) in normal and low-oxygen environments. These data indicate that, in the process of cardiac adaptation, left ventricular twist may play an important role that is not related to generating a larger output. Since enlarged hearts with low output can develop in disease, the present findings may influence the future interpretation of heart muscle function in patients. Despite increased stroke volume (SV), 'athlete's heart' has been proposed to have a similar left ventricular (LV) muscle function - as represented by LV twist - compared with the untrained state. However, the underpinning mechanisms and the associations between SV/cardiac output and LV twist during exercise are unknown. We hypothesised that endurance athletes would have a significantly lower twist-to-shortening ratio (TwSR, a parameter that relates twist to the shortening of heart muscle layers) at rest, but significantly greater LV muscle function during exercise. Eleven endurance trained male runners and 13 untrained males were tested at rest and during supine cycling exercise in normoxia and hypoxia (increased cardiac output but unaltered SV). Despite the expected cardiac remodelling in endurance athletes, LV twist, torsion, TwSR, strain and strain rate ('LV systolic mechanics') did not differ significantly between groups (P>0.05). Structural remodelling, as per relative wall thickness, and LV twist did not correlate (r2 =0.04, P=0.33). In normoxia and hypoxia, exercise increased LV systolic mechanics in both groups (P<0.001), but with different relationships to SV and cardiac output. Conversely to our hypothesis, hearts of different size had similar LV systolic mechanics, suggesting that similar twist, torsion and TwSR at rest and during exercise irrespective of cardiac output may be an important mechanism in healthy hearts. We hypothesise that the regulatory 'purpose' of LV twist may be related to the sensing of maximal cardiac myofibre stress, which may act as a biologically purposeful limiter to contraction.

No Difference between Spray Dried Milk and Native Whey Supplementation with Strength Training.

ABSTRACTBackgroundA rapid digestibility and high leucine content are considered important for maximal stimulation of muscle protein synthesis. Consequently, with these properties, native whey may hold greater anabolic potential than milk, when supplemented in combination with strength training. Our aim was to compare the effects of supplementation with milk or native whey, during a 12-wk strength training period, on gains in muscle mass and strength in young adults.MethodsIn this double-blinded, randomized, controlled study a total of 40 untrained young men and women received two daily servings of either milk or native whey containing 20 g of protein, during a 12-wk strength training intervention. Muscle strength, lean mass, thigh muscle cross-sectional area, m. vastus lateralis thickness and muscle fiber cross-sectional area were assessed before and after the training period. In addition, the acute phosphorylation of the anabolic kinases p70S6K, 4E-BP1 and eEF-2 in response to a standardized workout and supplementation was investigated before and after the 12-wk training period.ResultsMuscle mass and strength increased, by all measures applied (5%–16%, P < 0.001), with no differences between groups (P > 0.25). p70S6K phosphorylation increased (~1000%, P < 0.02) 2 h after exercise in the untrained and trained state, but no differences in anabolic signaling were observed between supplements (P > 0.40). No correlation between these acute measures and changes in muscle mass or strength were observed.ConclusionSupplementation with milk or native whey during a 12-wk strength training period did not differentially affect muscle mass and strength in young untrained individuals.

Exercise Training in Standardbred Horses Alters the Skeletal Muscle Metabolome and Plasma Amino Acid Profile: Implications for the “Athlete's Paradox”

To date equine skeletal muscle metabolism has centered on a limited number of candidate metabolites. As such, there is a dearth of information regarding global changes in skeletal muscle metabolism following exercise training. Thus, the purpose of this study was to determine the effects of exercise training on skeletal muscle metabolism through changes in the skeletal muscle metabolome in healthy, untrained Standardbred horses. In addition, we aimed to determine the extent to which protein metabolism is also altered through changes in the concentrations of plasma amino acids (AA). We hypothesized that training would significantly alter the skeletal muscle metabolome, as well as protein metabolism, as reflected in changes in the plasma AA profile. Eight untrained, Standardbred horses (n=4 mares, n=4 geldings; 3–9 yrs; 485 ± 13 kg, mean ± S.E.) underwent a 12‐week training program that significantly increased VO2 and exercise capacity (p&lt;0.05). Percutaneous needle biopsies were obtained from the M. gluteus medius in the untrained state (UT) and again following training (TR). Frozen muscle samples were submitted to Metabolon, Inc. for global metabolite profiling via UHPLC‐MS/MS. Blood obtained via jugular venipuncture was placed into EDTA tubes for the measurement of plasma AA concentrations via HPLC. For metabolomics analysis, differences between UT and TR samples were evaluated by two way‐ANOVA and Welch's t‐test for paired comparisons and considered significant at p&lt;0.05. For plasma AAs, differences were analyzed via Student's t‐test and considered significant at p&lt;0.05. Training resulted in significant alterations in lipid, branched‐chain amino acid (BCAA), and nucleotide metabolite classes in skeletal muscle. Of note, analysis revealed significant increases in the relative abundance of almost every identified FFA and complex lipid species in TR compared to UT muscle (p&lt;0.05), particularly the long‐chain (LC)‐acylcarnitines and diacylglycerides (DAGs) (1.5 to 2.3‐fold increases). Further, TR muscle exhibited increased fold‐changes (1.2 to 4.2‐fold) of C4 and several C5 BCAA‐derived acylcarnitines compared to UT (p&lt;0.05). In plasma, training caused a significant 36% increase in the concentration of total essential AAs (p&lt;0.05), of which and interestingly there was a significant increase in total BCAAs (42%, p&lt;0.05) and phenylalanine (27%, p&lt;0.05). In conclusion, exercise training significantly increased blood concentrations of total EAAs and BCAAs alongside significant increases in the relative abundances of certain skeletal muscle metabolites (i.e. LC‐acylcarnitines, BCAA‐derived acylcarnitines, and DAGs) that have been shown to be elevated during obesity and are proposed to play a role in the development of insulin resistance. These data underscore the complex nature of static metabolic signatures and the role that certain metabolites play in mediating health and disease. Future research should aim to utilize other sophisticated techniques that can address issues of metabolite flux and tissue utilization.Support or Funding InformationThis research was supported by: the New Jersey Institute for Food, Nutrition and Health (IFNH), USDA NIFA (NC 1184), the Rutgers University Equine Science Center (ESC), and the New Jersey Agriculture Experiment Station (NJAES).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Low-fat diet, and medium-fat diets containing coconut oil and soybean oil exert different metabolic effects in untrained and treadmill-trained mice

BackgroundDiets containing fats of different proportions and types have been demonstrated to influence metabolism. These fats differ in long chain fatty acids (LCFAs) or medium chain fatty acids (MCFAs) content. In our laboratory using swimming as the training modality, MCFAs increased endurance attributed to increased activities of oxidative enzymes. How it affects whole-body metabolism remains unexplored. The present study investigated the metabolic, biochemical and genetic adaptations with treadmill running as the training modality.MethodsC57BL/6N mice were divided into untrained and trained groups and provided with low-fat (10% kcal from soybean oil), coconut oil (10% kcal from soybean oil, 20% kcal from coconut oil) or soybean oil (30% kcal from soybean oil) diet. Training was performed on a treadmill for 30 days. After recovery, whole-body metabolism at rest and during exercise, endurance, substrate metabolism, mitochondrial enzyme activities, and gene expression of training-adaptive genes in the muscle and liver were measured.ResultsAt rest, medium-fat diets decreased respiratory exchange ratio (RER) (p < 0.05). Training increased RER in all diet groups without affecting oxygen consumption (p < 0.05). During exercise, diets had no overt effects on metabolism while training decreased oxygen consumption indicating decreased energy expenditure (p < 0.05). Coconut oil without training improved endurance based on work (p < 0.05). Training improved all endurance parameters without overt effects of diet (p < 0.05). Moreover, training increased the activities of mitochondrial enzymes likely related to the increased expression of estrogen related receptor (ERR) α and ERRβ (p < 0.05). Coconut oil inhibited peroxisome proliferator-activated receptor (PPAR) β/δ activation and glycogen accumulation in the muscle but activated PPARα in the liver in the trained state (p < 0.05). Substrate utilization data suggested that coconut oil and/or resulting ketone bodies spared glycogen utilization in the trained muscle during exercise thereby preserving endurance.ConclusionOur data demonstrated the various roles of diet and fat types in training adaptation. Diets exerted different roles in PPAR activation and substrate handling in the context of endurance exercise training. However, the role of fat types in training adaptations is limited as training overwhelms and normalizes the effects of diet in the untrained state particularly on endurance performance, mitochondrial biogenesis, and ERR expression.

Resistance training status modifies inflammatory response to explosive and hypertrophic resistance exercise bouts.

The purpose of the present study was to examine the immediate and prolonged immune response in circulating cytokine and adipocytokine concentrations after two different resistance exercise bouts: hypertrophic (HYP1, 5×10, 80% of 1RM) and maximal explosive (POW1, 10×5, 60% of 1RM) resistance exercise bouts and how 12weeks of resistance training (RT) modifies these responses (HYP2, POW2). Eight men completed the study. RE-induced interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), monocyte-chemoattractant protein-1 (MCP-1), leptin, resistin, and adiponectin were measured before (PRE) and immediately (POST0), 24 (POST24) and 48 (POST48) hours after RE bouts before and after RT. In the untrained state, IL-6 increased immediately after RE in HYP1 (p=0.002) and in POW1 (p=0.003) whereas no changes were observed after RT. Similar results were observed in IL-1β, whereas conversely, IL-1ra increased only after RT in HYP2 and POW2 (p<0.05). Resistin increased before RT in HYP1 and in POW1 (p=0.011 and p=0.003, respectively), but after RT, significant responses were not observed. Interestingly, in HYP2, MCP-1 increased significantly at POST24 (p=0.009) and at POST48 (p=0.032) only following RT. The present study shows that RT modifies RE-induced cytokine responses towards an anti-inflammatory direction.

Specific circulating phospholipids, acylcarnitines, amino acids and biogenic amines are aerobic exercise markers.

Regular aerobic exercise provides beneficial effects on human health and reduces all-cause mortality. Aerobic exercise has profound metabolic effects, and specific metabolites may reflect physiological changes. We aimed to identify endogenous metabolites that distinguish the trained from the untrained state to increase the spectrum of analytes amenable for hypothesis testing and to expand understanding of putative beneficial pathways. Cross sectional laboratory repeated measures study. Exercise testing was performed in 37 healthy male participants and serum samples were obtained before and after completion of a ten-week standardized exercise program. Samples were analyzed for routine clinical parameters and for 188 endogenous metabolites by LC-MS/MS. Indicating the effectiveness of the intervention program, parameters of sport physiology were different after training. After correcting for multiple testing, serum concentrations of several metabolites differed between the trained and untrained state. Serine and glutamate decreased in response to exercise, whereas sarcosine and kynurenine increased. Phosphatidylcholines showed a mixed response in that four species increased and three decreased. However, all seven lysophosphatidylcholines and all four plasmalogens that differed between the trained and untrained state, increased. One short-chain acylcarnitine also decreased. In receiver operator characteristics analyses, sarcosine displayed the highest AUC value (0.839; 95% CI: 0.734-0.926) in discriminating the pre- from the post-trained state. Our study detected metabolites that clearly differentiate the trained from the untrained state. These metabolites may be targeted in mechanistic studies to understand underlying biochemical pathways and could serve to improve the design, monitoring and individualization of training programs.

Specific circulating phospholipids, acylcarnitines, amino acids and biogenic amines are aerobic exercise markers

Abstract Objectives Regular aerobic exercise provides beneficial effects on human health and reduces all-cause mortality. Aerobic exercise has profound metabolic effects, and specific metabolites may reflect physiological changes. We aimed to identify endogenous metabolites that distinguish the trained from the untrained state to increase the spectrum of analytes amenable for hypothesis testing and to expand understanding of putative beneficial pathways. Design Cross sectional laboratory repeated measures study. Methods Exercise testing was performed in 37 healthy male participants and serum samples were obtained before and after completion of a ten-week standardized exercise program. Samples were analyzed for routine clinical parameters and for 188 endogenous metabolites by LC–MS/MS. Results Indicating the effectiveness of the intervention program, parameters of sport physiology were different after training. After correcting for multiple testing, serum concentrations of several metabolites differed between the trained and untrained state. Serine and glutamate decreased in response to exercise, whereas sarcosine and kynurenine increased. Phosphatidylcholines showed a mixed response in that four species increased and three decreased. However, all seven lysophosphatidylcholines and all four plasmalogens that differed between the trained and untrained state, increased. One short-chain acylcarnitine also decreased. In receiver operator characteristics analyses, sarcosine displayed the highest AUC value (0.839; 95% CI: 0.734–0.926) in discriminating the pre- from the post-trained state. Conclusions Our study detected metabolites that clearly differentiate the trained from the untrained state. These metabolites may be targeted in mechanistic studies to understand underlying biochemical pathways and could serve to improve the design, monitoring and individualization of training programs.

Cycle training modulates satellite cell and transcriptional responses to a bout of resistance exercise.

This investigation evaluated whether moderate‐intensity cycle ergometer training affects satellite cell and molecular responses to acute maximal concentric/eccentric resistance exercise in middle‐aged women. Baseline and 72 h postresistance exercise vastus lateralis biopsies were obtained from seven healthy middle‐aged women (56 ± 5 years, BMI 26 ± 1, VO 2max 27 ± 4) before and after 12 weeks of cycle training. Myosin heavy chain (MyHC) I‐ and II‐associated satellite cell density and cross‐sectional area was determined via immunohistochemistry. Expression of 93 genes representative of the muscle‐remodeling environment was also measured via NanoString. Overall fiber size increased ~20% with cycle training (P = 0.052). MyHC I satellite cell density increased 29% in response to acute resistance exercise before endurance training and 50% with endurance training (P < 0.05). Following endurance training, MyHC I satellite cell density decreased by 13% in response to acute resistance exercise (acute resistance × training interaction, P < 0.05). Genes with an interaction effect tracked with satellite cell behavior, increasing in the untrained state and decreasing in the endurance trained state in response to resistance exercise. Similar satellite cell and gene expression response patterns indicate coordinated regulation of the muscle environment to promote adaptation. Moderate‐intensity endurance cycle training modulates the response to acute resistance exercise, potentially conditioning the muscle for more intense concentric/eccentric activity. These results suggest that cycle training is an effective endurance exercise modality for promoting growth in middle‐aged women, who are susceptible to muscle mass loss with progressing age.

Aquatic Treadmill Exercise Combined With Resistance Exercise Yields Different Cytokine Responses Compared To Land Treadmill

We have previously shown that aquatic treadmill (ATM) running may alter acute inflammatory responses when performed after resistance exercise (RT). PURPOSE: To investigate the effects of RT alone and combined with either land treadmill (RT-LTM) or ATM exercise (RT-ATM) on TNFα, IL-6, IL-8, IL-10, INFg, and GMCSF. METHODS: Forty-seven untrained men (n=23, 37±11yrs, 182.7±6.7cm, 98.9±16.1kg) and women (n=24, 38±12yrs, 165.6±4.8cm, 82.1±19.1kg) were randomized into three groups: RT-LTM, RT-ATM, and RT, then assigned progressive RT (2/wk, 3 x 8-12 repetitions, 60◊85% 1RM) for 12wk. The RT-ATM and RT-LTM groups progressively added ATM or LTM immediately following RT sessions and in isolation on a 3rd day to total up to 500 kcal/bout. Muscular strength, body composition, and VO2max were measured before and after training. Fasting blood samples were obtained before and 24h after acute exercise before and after training for analysis serum cytokines. A 3(group) x 2(time) mixed model ANCOVAs (covaried on baseline values) were used to detect acute changes in serum cytokines and chronic changes in VO2max, strength, and body composition (α=0.05). RESULTS: In the untrained state, acute RT-LTM exercise was found to significantly increase IL-6 (+71.04% ±31.23). Acute RT-ATM exercise yielded greater increases in IL-10 in the untrained state (+44.11% ±18.41) than RT-LTM (-1.15% ±13.39). Additionally, acute RT-ATM exercise was observed to increase INFg in the untrained state (+111.42% ±48.55). In the trained state, RT-ATM exercise elicited a greater increase in IL-10 (+67.77% ±21.72) than RT-LTM (-2.81% ±10.77) and RT (-4.29% ±9.45). All groups were found to have significant increases in total strength with RT-ATM (+608.53lbs ±75.0) eliciting a greater increase than RT-LTM (+364.38lbs ±39.0) and RT (+432.78lbs ±46.0). All groups were found to have significant increases in VO2max with RT-LTM (+2.79ml/kg/min ±0.6), RT-ATM (+3.36 ml/kg/min ±0.6), and RT (+5.85 ml/kg/min ±0.7) being statistically different from the other. Both RT-ATM (-1.71 ±0.4) and RT-LTM (-2.79 ±0.4) exercise were found to decrease body fat. CONCLUSION: Cytokine responses related to pro-inflammatory, anti-inflammatory, and metabolic signaling are mode dependent and may affect training adaptations.

Response.

Dear Editor-in-Chief We appreciate the interest of such influential colleagues in our recent meta-analysis (5). Point-by-point responses to their comments are presented below: In our view, experts in meta-analysis concur that “The Cochrane Risk of Bias Assessment” tool is designed to evaluate randomized controlled trials, which have yet to be performed on the topic of the current meta-analysis. Likewise, PRISMA, but not MOOSE, guidelines focus on randomized controlled trials. An identical comment concerning arteriovenous oxygen difference (a-vO2diff) is acknowledged and fully addressed in the manuscript. The training study of Roca et al. (8) reported neither maximal cardiac output (max) nor a-vO2diff (i.e., the outcomes required for the present meta-analysis); therefore, that study cannot be included. Of note, the process of article selection is straightforward and thoroughly described (5).We concur with the prevailing notion that any variable potentially influenced by exercise training (ExT) may be modified more with ExT in untrained versus trained individuals. If, however, such a variable (e.g., a-vO2diff at maximal exercise) is close to optimal levels in the untrained state, ExT will induce a less marked effect. This conjecture is firmly opposed by “the null heterogeneity among studies and the associations between the standardized mean differences (SMDs) in max and V˙O2max (P = 0.006), and the SMD in a-vO2diff and duration of training (P = 0.0002)” ([5], p. 2031). To relieve our colleagues’ main concern, the meta-analysis reveals that a-vO2diff is indeed increased with ExT, when this lasts 12 or more weeks (5). This finding has also been observed in healthy age individuals (4). With shorter (5–11 wk) ExT duration, max, but not a-vO2diff, is increased irrespective of age, according to 18 studies comprising nearly 200 individuals (4,5). Moreover, Poole et al. (7) seem to ignore solid human experimental proof demonstrating that the increase in V˙O2max with short-term (6 wk) ExT is abolished when the increase in max is manipulated to pretraining values—despite the presence of skeletal muscle adaptations, including increases in capillarization and mitochondrial content (3). Poole et al. (7) appear to perceive a-vO2diff as an equivalent of muscle O2 diffusing capacity (DO2m), which it is not. DO2m is computed as V˙O2 divided by the muscle O2 pressure gradient (9); thus, it is intrinsically determined by strict muscle O2 diffusing capacity and convective O2 delivery, which in turn is primarily a function of muscle blood flow. Accordingly, it cannot be discarded that DO2m increases with ExT are essentially the consequence of enhanced max leading to augmented muscle blood flow. In addition, our colleagues seem to rely on a theoretical model (9) based on untenable assumptions (6) to speculate that any potential increase in V˙O2max should, at least in part, be limited by skeletal muscle attributes determining DO2m. The collapse of their model is strikingly evident, considering the aforementioned unequivocal evidence (3) and experimental data gathered for a century in humans and other vertebrates (2). Furthermore, recent (again apparently unnoticed) catheterization studies demonstrate a twofold functional reserve in DO2m at V˙O2max in healthy untrained individuals (1). Ultimately, caution should be exercised before proposing therapeutic interventions only targeting skeletal muscle adaptations if attempting to improve V˙O2max substantially. David Montero Zurich Center for Integrative Human Physiology Institute of Physiology, University of Zurich Zurich, SWITZERLAND Candela Diaz-Cañestro Center for Molecular Cardiology University of Zurich Schlieren, SWITZERLAND Carsten Lundby Zurich Center for Integrative Human Physiology Institute of Physiology, University of Zurich Zurich, SWITZERLAND