Acute and long-term exercise adaptation of adipose tissue and skeletal muscle in humans: a matched transcriptomics approach after 8-week training-intervention.

BACKGROUND: Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention of metabolic diseases. AIM: To characterize the response of human SCAT based on changes in transcripts and mitochondrial respiration to acute and repeated bouts of exercise in comparison to skeletal muscle. METHODS: Sedentary participants (27 ± 4 yrs) with overweight or obesity underwent 8-week supervised endurance exercise 3×1h/week at 80% VO2peak. Before, 60 min after the first and last exercise bout and 5 days post intervention, biopsies were taken for transcriptomic analyses and high-resolution respirometry (n = 14, 8 female/6 male). RESULTS: In SCAT, we found 37 acutely regulated transcripts (FC > 1.2, FDR < 10%) after the first exercise bout compared to 394, respectively, in skeletal muscle. Regulation of only 5 transcripts overlapped between tissues highlighting their differential response. Upstream and enrichment analyses revealed reduced transcripts of lipid uptake, storage and lipogenesis directly after exercise in SCAT and point to ß-adrenergic regulation as potential major driver. The data also suggest an exercise-induced modulation of the circadian clock in SCAT. Neither term was associated with transcriptomic changes in skeletal muscle. No evidence for beigeing/browning was found in SCAT along with unchanged respiration. CONCLUSIONS: Adipose tissue responds completely distinct from adaptations of skeletal muscle to exercise. The acute and repeated reduction in transcripts of lipid storage and lipogenesis, interconnected with a modulated circadian rhythm, can counteract metabolic syndrome progression toward diabetes.

The Acute Cytokine Response to 30-Minute Exercise Bouts Before and After 8-Week Endurance Training in Individuals With Obesity.

CONTEXT: One acute bout of exercise leads to a rapid increase in the systemic cytokine concentration. Regular exercise might alter the cytokine response, in particular in beforehand untrained and obese individuals. OBJECTIVE: Using a proximity extension assay, we studied the effects of acute exercise as well as endurance training on a panel of 92 cytokines related to inflammation. METHODS: A total of 22 individuals (30 ± 9 years; peak oxygen uptake [VO2peak] 25.2 ± 4.2 mL/[kg × min]; body mass index [BMI] 31.7 ± 4.4) participated in an 8-week endurance exercise intervention. Blood samples were collected before and immediately after 30 minutes' ergometer exercise at 80% VO2peak. RESULTS: Before and after the training intervention, 40 and 37 cytokines, respectively, were acutely increased more than 1.2-fold (Benjamini-Hochberg [BH]-adjusted P < .05). The exercise intervention did not change the acute increase in cytokines nor the resting cytokine levels, whereas fitness was improved and adiposity reduced. The increase in fitness led to a slight increase in power output when exercising at the same heart rate, which might explain the comparable increase in cytokines before and after the intervention. The largest acute increase was found for OSM, TGFA, CXCL1 and 5, and TNFSF14 (≥ 1.9-fold, BH-adjusted P < .001). The transcript levels of these proteins in whole blood were also elevated, particularly in the trained state. Only the acute increase in IL6 (1.3-fold) was related to the increase in lactate, confirming the lactate-driven secretion of IL6. CONCLUSION: Our comprehensive proteomics approach detected several underexplored serum exerkines with up to now less understood function in the adaptation to exercise.

Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese.

BACKGROUNDInsulin resistance of the brain can unfavorably affect long-term weight maintenance and body fat distribution. Little is known if and how brain insulin sensitivity can be restored in humans. We aimed to evaluate the effects of an exercise intervention on insulin sensitivity of the brain and how this relates to exercise-induced changes in whole-body metabolism and behavior.METHODSIn this clinical trial, sedentary participants who were overweight and obese underwent an 8-week supervised aerobic training intervention. Brain insulin sensitivity was assessed in 21 participants (14 women, 7 men; age range 21-59 years; BMI range 27.5-45.5 kg/m2) using functional MRI, combined with intranasal administration of insulin, before and after the intervention.RESULTSThe exercise program resulted in enhanced brain insulin action to the level of a person of healthy weight, demonstrated by increased insulin-induced striatal activity and strengthened hippocampal functional connectivity. Improved brain insulin action correlated with increased mitochondrial respiration in skeletal muscle, reductions in visceral fat and hunger, as well as improved cognition. Mediation analyses suggest that improved brain insulin responsiveness helps mediate the peripheral exercise effects leading to healthier body fat distribution and reduced perception of hunger.CONCLUSIONOur study demonstrates that an 8-week exercise intervention in sedentary individuals can restore insulin action in the brain. Hence, the ameliorating benefits of exercise toward brain insulin resistance may provide an objective therapeutic target in humans in the challenge to reduce diabetes risk factors.TRIAL REGISTRATIONClinicalTrials.gov (NCT03151590).FUNDINGBMBF/DZD 01GI0925.

Fatigue Prediction in Outdoor Running Conditions using Audio Data.

Although running is a common leisure activity and a core training regiment for several athletes, between 29% and 79% of runners sustain an overuse injury each year. These injuries are linked to excessive fatigue, which alters how someone runs. In this work, we explore the feasibility of modelling the Borg received perception of exertion (RPE) scale (range: [6]-[19] [20]), a well-validated subjective measure of fatigue, using audio data captured in realistic outdoor environments via smartphones attached to the runners' arms. Using convolutional neural networks (CNNs) on log-Mel spectrograms, we obtain a mean absolute error (MAE) of 2.35 in subject-dependent experiments, demonstrating that audio can be effectively used to model fatigue, while being more easily and non-invasively acquired than by signals from other sensors.

Effect of Two Different Training Interventions on Cycling Performance in Mountain Bike Cross-Country Olympic Athletes.

To improve performance in endurance sports, it is important to include both high-intensity and low-intensity training, but there is neither a universally accepted practice nor clear scientific evidence that allows reliable statements about the predominance of a specific training method. This randomized controlled trial compared the effects of a polarized training model (POL) to a low-intensity training model (LIT) on physiological parameters and mountain bike cross-country Olympic (XCO) race performance in eighteen competitive XCO athletes (17.9 ± 3.6 years). The superiority of one of the two methods could not be shown in this study. The results did not show statistically significant differences between POL and LIT, as both interventions led to slight improvements. However, a small tendency toward better effects for POL was seen for cycling power output during the race (4.4% vs. -2.2%), at the 4 mmol/L (6.1% vs. 2.8%) and individual anaerobic lactate threshold (5.1% vs. 2.3%), and for maximal aerobic performance (4.4% vs. 2.6%), but not for maximal efforts lasting 10 to 300 s. Despite the lack of significant superiority in this and some other studies, many athletes and coaches prefer POL because it produces at least equivalent effects and requires less training time.

Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects.

CONTEXT: Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. OBJECTIVE: To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. DESIGN: Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). RESULTS: Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (>15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for ß-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. CONCLUSION: Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue.

Cycling Performance in Short-term Efforts: Laboratory and Field-Based Data in XCO Athletes.

Mountain bike cross-country Olympic has an intermittent performance profile, underlining the importance of short-term but high cycling power output. Previous findings indicate that power output during sprint tests differs between laboratory and field-based conditions and that cycling cadence rises with increasing workload. The aim was therefore to examine power output and cadence in short-term efforts under laboratory and field conditions. Twenty-three competitive athletes (17.9±3.7 years) performed a laboratory power profile test and a simulated race within one week. Power output and cadence during the power profile test were compared to corresponding short-term efforts during the race over durations of 10-300s (TT 10-300 ). Differences were TT 10 +8%, TT 30 +7%, TT 60 -15% and TT 300 -12% for power output and+10%,+8%,+19%,+21% for cadence respectively. Compared to the race, we found higher power output during the power profile test for the shorter efforts but lower for TT 60 and TT 300 . Confirming previous results, cadence was higher during the power profile test compared to the respective intervals of the race and increased with increasing workload or shorter time trial duration. Future research should take into account that compared to the field, a higher cadence is used in laboratory settings to produce similar power output.

Predictive Ability of a Laboratory Performance Test in Mountain Bike Cross-country Olympic Athletes.

Mountain bike Cross-Country Olympic (XCO) has an intermittent performance profile, underlining the importance of anaerobic metabolism. Traditional performance tests in cycling primarily quantify aerobic metabolism and inadequately meet the demands in XCO. The aim was therefore to validate a specific test that quantifies these requirements by means of an XCO race.Twenty-three competitive XCO athletes (17.9±3.6 years) performed a previously developed performance test and an XCO race within one week. Correlations between individual anaerobic threshold (IAT), 4 mmol lactate threshold (LT4), maximal aerobic power (MAP), maximal effort time trials (TT) for 10-300 s and mean power output of the race (POR) were calculated. In addition, a multiple regression model of the predictive value of the test was calculated.Variables correlated significantly (p<.01) with POR: IAT (r=.81), LT4 (r=0.79), MAP (r=0.91), TT10 (r=0.75), TT30 (r=0.85), TT60 (r=0.84) and TT300 (r=0.86). In the regression model, sex and body mass were set influencing variables (R²adj.=0.70), whereby MAP had the highest correlation with POR and significantly improved the predictive value of the model (R²adj.=0.86).The high correlation of collected performance variables with POR indicated the MTB-PT's additional benefit for performance testing in XCO because it is specific but very feasible.

The neurobiology of placebo effects in sports: EEG frontal alpha asymmetry increases in response to a placebo ergogenic aid.

The performance enhancing (ergogenic) placebo effect is elicited by an inert treatment and caused by positive affective appraisal of effort perception. Frontal alpha asymmetry (FAA) is a neurobiological correlate of positive affect. This study investigates, whether receiving an ergogenic placebo increases FAA and whether scores on the behavioral inhibition and activation system (BIS/BAS) scales affect this increase in FAA. Nineteen competitive male cyclists (37.26 ± 9.82 years) performed two maximum effort time trials. The first served as baseline for the second intervention time trial, where athletes received a placebo ergogenic aid or no treatment. We recorded FAA using EEG throughout all time trials and assessed BIS/BAS by questionnaire. There was a significant difference in change from baseline to intervention time trial in FAA during cycling in response to the placebo ergogenic aid compared to the control group. BIS, the BAS subscale Drive and the BAS-BIS difference score significantly co-varied with the change in FAA from baseline to intervention time trial in response to the placebo ergogenic aid. Administering a placebo ergogenic aid significantly influenced FAA during maximum effort cycling. Those athletes with a more pronounced goal seeking persistence and an overall dominance of the BAS over the BIS showed a significantly greater increase in FAA in response to a placebo ergogenic aid. A more pronounced BIS, however, seems to antagonize the increase in FAA associated with the ergogenic placebo response.

Increasing effort without noticing: A randomized controlled pilot study about the ergogenic placebo effect in endurance athletes and the role of supplement salience.

PURPOSE: Previous research shows that endurance performance can be enhanced by placebo ergogenic aids. This study investigates the ergogenic placebo response, which we define as an increase in objective and physiological effort without an increase in subjective effort, in competitive cyclists. The primary objective of this study is to explore the role of supplement salience in the ergogenic placebo response, while the secondary aim is to assess whether believing to have taken an inactive placebo supplement attenuates the desired ergogenic effect. METHODS: We employed a double-blind placebo-controlled study design and compared a high salience (pudding) to a low salience (capsules) ergogenic placebo supplement and to a no treatment control group. Thirty-four male athletes (30.0 ± 5.7 years) performed two self-regulated time trials on an isokinetic cycling ergometer, one without intervention serving as a baseline and one with intervention according to group assignment. At both time trials, power output (objective effort), blood lactate (physiological effort) and the rating of perceived exertion (subjective effort) were measured. RESULTS: Receiving a high salience supplement can increase physiological and objective effort without a proportional rise in subjective effort, suggesting a decoupling of perceived exertion and endurance performance. Low salience and control group both showed no such ergogenic placebo response. Athletes' belief concerning the true nature of the ergogenic aid (inactive placebo vs. ergogenic supplement) did not influence the ergogenic placebo response. CONCLUSION: High salience placebo ergogenic aids can elicit enhanced performance without the athlete noticing (exertion), and deception of athletes seems unnecessary as even believing to have received an inactive placebo supplement maintains the ergogenic placebo response.

Predictive ability of a comprehensive incremental test in mountain bike marathon.

OBJECTIVES: Traditional performance tests in mountain bike marathon (XCM) primarily quantify aerobic metabolism and may not describe the relevant capacities in XCM. We aimed to validate a comprehensive test protocol quantifying its intermittent demands. METHODS: Forty-nine athletes (38.8±9.1 years; 38 male; 11 female) performed a laboratory performance test, including an incremental test, to determine individual anaerobic threshold (IAT), peak power output (PPO) and three maximal efforts (10 s all-out sprint, 1 min maximal effort and 5 min maximal effort). Within 2 weeks, the athletes participated in one of three XCM races (n=15, n=9 and n=25). Correlations between test variables and race times were calculated separately. In addition, multiple regression models of the predictive value of laboratory outcomes were calculated for race 3 and across all races (z-transformed data). RESULTS: All variables were correlated with race times 1, 2 and 3: 10 s all-out sprint (r=-0.72; r=-0.59; r=-0.61), 1 min maximal effort (r=-0.85; r=-0.84; r=-0.82), 5 min maximal effort (r=-0.57; r=-0.85; r=-0.76), PPO (r=-0.77; r=-0.73; r=-0.76) and IAT (r=-0.71; r=-0.67; r=-0.68). The best-fitting multiple regression models for race 3 (r2=0.868) and across all races (r2=0.757) comprised 1 min maximal effort, IAT and body weight. CONCLUSION: Aerobic and intermittent variables correlated least strongly with race times. Their use in a multiple regression model confirmed additional explanatory power to predict XCM performance. These findings underline the usefulness of the comprehensive incremental test to predict performance in that sport more precisely.

Functional brain imaging of walking while talking - An fNIRS study.

Since functional imaging of whole body movements is not feasible with functional magnetic resonance imaging (fMRI), the present study presents in vivo functional near-infrared spectroscopy (fNIRS) as a suitable technique to measure body movement effects on fronto-temporo-parietal cortical activation in single- and dual-task paradigms. Previous fNIRS applications in studies addressing whole body movements were typically limited to the assessment of prefrontal brain areas. The current study investigated brain activation in the frontal, temporal and parietal cortex of both hemispheres using functional near-infrared spectroscopy (fNIRS) with two large 4×4 probe-sets with 24 channels each during single and dual gait tasks. 12 young healthy adults were measured using fNIRS walking on a treadmill: the participants performed two single-task (ST) paradigms (walking at different speeds, i.e. 3 and 5km/h) and a dual task (DT) paradigm where a verbal fluency task (VFT) had to be executed while walking at 3km/h. The results show an increase of activation in Broca's area during the more advanced conditions (ST 5km/h vs. ST 3km/h, DT vs. ST 3km/h, DT vs. 5km/h), while the corresponding area on the right hemisphere was also activated. DT paradigms including a cognitive task in conjunction with whole body movements elicit wide-spread cortical activation patterns across fronto-temporo-parietal areas. An elaborate assessment of these activation patterns requires more extensive fNIRS assessments than the traditional prefrontal investigations, e.g. as performed with portable fNIRS devices.

TGF-ß Contributes to Impaired Exercise Response by Suppression of Mitochondrial Key Regulators in Skeletal Muscle.

A substantial number of people at risk of developing type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals at high risk of developing type 2 diabetes who performed 8 weeks of controlled cycling and walking training at 80% individual Vo2 peak. Participants identified as nonresponders in insulin sensitivity (based on the Matsuda index) did not differ in preintervention parameters compared with high responders. The failure to increase insulin sensitivity after training correlates with impaired upregulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1α and AMPKα2. The muscle transcriptomes of the nonresponders are further characterized by the activation of transforming growth factor (TGF)-ß and TGF-ß target genes, which is associated with increases in inflammatory and macrophage markers. TGF-ß1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGF-ß1 signaling downregulates the abundance of PGC1α, AMPKα2, the mitochondrial transcription factor TFAM, and mitochondrial enzymes. Thus, the data suggest that increased TGF-ß activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity.