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Van Thienen R.,Catholic University of Leuven | Masschelein E.,Catholic University of Leuven | D'Hulst G.,Catholic University of Leuven | Thomis M.,Sports and Health Research Group | Hespel P.,Catholic University of Leuven
Frontiers in Physiology | Year: 2017

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of myocellular adaptation to exercise and hypoxia. However, the role of genetic factors in regulation of HIF-1 responses to exercise and hypoxia is unknown. We hypothesized that hypoxia at rest and during exercise stimulates the HIF-1 pathway and its downstream targets in energy metabolism regulation in a genotype-dependent manner. Eleven monozygotic twin (MZ) pairs performed an experimental trial in both normoxia and hypoxia (FiO2 10.7%). Biopsies were taken from m. vastus lateralis before and after a 20-min submaximal cycling bout @~30% of sea-level VO2max. Key-markers of the HIF-1 pathway and glycolytic and oxidative metabolism were analyzed using real-time PCR and Western Blot. Hypoxia increased HIF-1α protein expression by ~120% at rest vs. +150% during exercise (p < 0.05). Furthermore, hypoxia but not exercise increased muscle mRNA content of HIF-1α (+50%), PHD2 (+45%), pVHL (+45%; p < 0.05), PDK4 (+1200%), as well as PFK-M (+20%) and PPAR-γ1 (+60%; p < 0.05). Neither hypoxia nor exercise altered PHD1, LDH-A, PDH-A1, COX-4, and CS mRNA expressions. The hypoxic, but not normoxic exercise-induced increment of muscle HIF-1α mRNA content was about 10-fold more similar within MZ twins than between the twins (p < 0.05). Furthermore, in resting muscle the hypoxia-induced increments of muscle HIF-1α protein content, and HIF-1α and PDK4 mRNA content were about 3-4-fold more homogeneous within than between the twins pairs (p < 0.05). The present observations in monozygotic twins for the first time clearly indicate that the HIF-1α protein as well as mRNA responses to submaximal exercise in acute hypoxia are at least partly regulated by genetic factors. © 2017 Van Thienen, Masschelein, D'Hulst, Thomis and Hespel.


Thomaes T.,Catholic University of Leuven | Thomis M.,Sports and Health Research Group | Onkelinx S.,Catholic University of Leuven | Goetschalckx K.,University Hospital Leuven | And 3 more authors.
Medicine and Science in Sports and Exercise | Year: 2013

INTRODUCTION: The number of studies trying to identify genetic sequence variation related to muscular phenotypes has increased enormously. The aim of this study was to identify the role of a genetic predisposition score (GPS) based on earlier identified gene variants for different muscular endophenotypes to explain the individual differences in muscular fitness characteristics and the response to training in patients with coronary artery disease. METHODS: Two hundred and sixty coronary artery disease patients followed a standard ambulatory, 3-month supervised training program for cardiac patients. Maximal knee extension strength (KES) and rectus femoris diameter were measured at baseline and after rehabilitation. Sixty-five single nucleotide polymorphisms (SNP) in 30 genes were selected based on genotype-phenotype association literature. Backward regression analysis revealed subsets of SNP associated with the different phenotypes. GPS were constructed for all sets of SNP by adding up the strength-increasing alleles. General linear models and multiple stepwise regression analysis were used to test the explained variance of the GPS in baseline and strength responses. Receiver operating characteristic curve analyses were performed to discriminate between high- and low-responder status. RESULTS: GPS were significantly associated with the rectus femoris diameter (P < 0.01) and its response (P < 0.0001), the isometric KES (P < 0.05) and its response (P < 0.01), the isokinetic KES at 60°s-1 (P < 0.05) and 180°s-1 (P < 0.001) and their responses to training (P < 0.0001), and the isokinetic KES endurance (P < 0.001) and its change after training (P < 0.0001). The GPS was shown as an independent determinant in baseline and response phenotypes with partial explained variance up to 23%. Receiver operating characteristic analysis showed a significant discriminating accuracy of the models, including the GPS for responses to training, with areas under the curve ranging from 0.62 to 0.85. CONCLUSION: GPS for muscular phenotypes showed to be associated with baseline KES, muscle diameter, and the response to training in cardiac rehabilitation patients. Copyright © 2013 by the American College of Sports Medicine.


PubMed | Ghent University, University of Cambridge, Sports and Health Research Group and Vrije Universiteit Brussel
Type: | Journal: British journal of sports medicine | Year: 2016

We aimed to study the independent associations of 10-year change in sedentary behaviour (SB), moderate-to-vigorous physical activity (MVPA) and objectively measured cardiorespiratory fitness (CRF), with concurrent change in clustered cardiometabolic risk and its individual components (waist circumference, fasting glucose, high-density lipoprotein (HDL) cholesterol, triglycerides and blood pressure). We also determined whether associations were mediated by change in CRF (for SB and MVPA), waist circumference (for SB, MVPA and CRF) and dietary intake (for SB).A population-based sample of 425 adults (age (meanSD) 55.839.40; 65% men) was followed prospectively for 9.620.52years. Participants self-reported SB and MVPA and performed a maximal cycle ergometer test to estimate peak oxygen uptake at baseline (2002-2004) and follow-up (2012-2014). Multiple linear regression and the product of coefficients method were used to examine independent associations and mediation effects, respectively.Greater increase in SB was associated with more detrimental change in clustered cardiometabolic risk, waist circumference, HDL cholesterol and triglycerides, independently of change in MVPA. Greater decrease in MVPA was associated with greater decrease in HDL cholesterol and increase in clustered cardiometabolic risk, waist circumference and fasting glucose, independent of change in SB. Greater decrease in CRF was associated with more detrimental change in clustered cardiometabolic risk and all individual components. Change in CRF mediated the associations of change in SB and MVPA with change in clustered cardiometabolic risk, waist circumference and, only for MVPA, HDL cholesterol. Change in waist circumference mediated the associations between change in CRF and change in clustered cardiometabolic risk, fasting glucose, HDL cholesterol and triglycerides.A combination of decreasing SB and increasing MVPA, resulting in positive change in CRF, is likely to be most beneficial towards cardiometabolic health.


PubMed | Ghent University and Sports and Health Research Group
Type: Journal Article | Journal: Journal of sports sciences | Year: 2016

Approximately 3.2 million people die of non-communicable diseases (NCD) each year due to insufficient physical activity. Physical activity guidelines are possibly perceived as too demanding and might thus pose a barrier. We addressed the question if a more stable physical activity pattern is associated with higher levels of health-related fitness than one with high and low intensities, regardless of the physical activity level (PAL). Physical activity was objectively measured in 296 men and women (53.78.94years) with the SenseWear Pro Armband


Broos S.,Exercise Physiology Research Group | Malisoux L.,Sports Medicine Research Laboratory | Theisen D.,Sports Medicine Research Laboratory | Francaux M.,Catholic University of Louvain | And 2 more authors.
PLoS ONE | Year: 2012

A common nonsense polymorphism in the ACTN3 gene results in the absence of α-actinin-3 in XX individuals. The wild type allele has been associated with power athlete status and an increased force output in numeral studies, though the mechanisms by which these effects occur are unclear. Recent findings in the Actn3-/- (KO) mouse suggest a shift towards 'slow' metabolic and contractile characteristics of fast muscle fibers lacking α-actinin-3. Skinned single fibers from the quadriceps muscle of three men with spinal cord injury (SCI) were tested regarding peak force, unloaded shortening velocity, force-velocity relationship, passive tension and calcium sensitivity. The SCI condition induces an 'equal environment condition' what makes these subjects ideal to study the role of α-actinin-3 on fiber type expression and single muscle fiber contractile properties. Genotyping for ACTN3 revealed that the three subjects were XX, RX and RR carriers, respectively. The XX carrier's biopsy was the only one that presented type I fibers with a complete lack of type IIx fibers. Properties of hybrid type IIa/IIx fibers were compared between the three subjects. Absence of α-actinin-3 resulted in less stiff type IIa/IIx fibers. The heterozygote (RX) exhibited the highest fiber diameter (0.121±0.005 mm) and CSA (0.012±0.001 mm2) and, as a consequence, the highest peak force (2.11±0.14 mN). Normalized peak force was similar in all three subjects (P = 0.75). Unloaded shortening velocity was highest in R-allele carriers (P<0.001). No difference was found in calcium sensitivity. The preservation of type I fibers and the absence of type IIx fibers in the XX individual indicate a restricted transformation of the muscle fiber composition to type II fibers in response to long-term muscle disuse. Lack of α-actinin-3 may decrease unloaded shortening velocity and increase fiber elasticity. © 2012 Broos et al.


Van Hoye K.,Sports and Health Research Group | Boen F.,Sports and Health Research Group | Lefevre J.,Sports and Health Research Group
International Journal of Environmental Research and Public Health | Year: 2015

Assessing levels of physical activity (PA) and providing feedback about these levels might have an effect on participant’s PA behavior. This study discusses the effect of different levels of feedback—from minimal to use of a feedback display and coach—on PA over a 4-week intervention period. PA was measured at baseline, during and immediately after the intervention. Participants (n = 227) were randomly assigned to a Minimal Intervention Group (MIG-no feedback), Pedometer Group (PG-feedback on steps taken), Display Group (DG-feedback on steps, minutes of moderate to vigorous physical activity and energy expenditure) or Coaching Group (CoachG-same as DG with need-supportive coaching). Two-way ANCOVA showed no significant Group × Time interaction effect for the different PA variables between the MIG and PG. Also no differences emerged between PG and DG. As hypothesized, CoachG had higher PA values throughout the intervention compared with DG. Self-monitoring using a pedometer resulted in more steps compared with a no-feedback condition at the start of the intervention. However, adding individualized coaching seems necessary to increase the PA level until the end of the intervention. © 2015 by the authors; licensee MDPI, Basel, Switzerland.


Objectives The aim of this study was to investigate the effect of a skill-focused BLS course on secondary school children’s self-reported willingness to and reasons not to perform BLS in real life and the relation of this willingness with simulated BLS performance. Methods 313 secondary school children (133 girls and 180 boys, age 12-18 years) constituting 18 classes received a standardized 50-min BLS course by their physical education teacher. Course content was delivered through the reciprocal peer learning model with iPads as instructional tools. Before and after the BLS course, children completed a questionnaire regarding their willingness and fear to perform BLS. Results About 50% of the children reported they would perform BLS on a family member or friend. 10% reported they would perform BLS on strangers. There were no significant differences before and after the course, except for boys who showed a significant increase in willingness to perform BLS on family members from 49% to 58%, P = 0.01. ‘Being unable’ as a reason for not performing BLS decreased significantly after the course as well as girls’ fear to perform mouth-to-mouth ventilation, P < 0.01. A significant positive correlation was found between the students’ willingness to perform BLS at pretest and their BLS performance, P = 0.02. Conclusion Children’s willingness to and reasons not to perform BLS in real life were largely unaffected by a skill-focused BLS course. Future research should investigate how the willingness to perform BLS can be increased and fears reduced during BLS courses in order to increase bystander BLS. © 2016, Acta Cardiologica. All rights reserved.


Masschelein E.,Catholic University of Leuven | Van Thienen R.,Catholic University of Leuven | Thomis M.,Sports and Health Research Group | Hespel P.,Catholic University of Leuven
Medicine and Science in Sports and Exercise | Year: 2015

Purpose: Physiological responses to hypoxia vary between individuals, and genetic factors are conceivably involved. Using a monozygotic twin design, we investigated the role of genetic factors in physiological responses to acute hypoxia. Methods: Thirteen pairs of monozygotic twin brothers participated in two experimental sessions in a normobaric hypoxic facility with a 2-wk interval. In one session, fraction of inspired O2 (FiO2) was gradually reduced to 10.7% (approximately 5300 m altitude) over 5 h. During the next 3 h at 10.7%, FiO2 subjects performed a 20-min submaximal exercise bout (EXSUB, 1.2 W·kg-1) and a maximal incremental exercise test (EXMAX). An identical control experiment was done in normoxia. Cardiorespiratory measurements were continuously performed, and 8-h urine output was collected. Results: Compared with normoxia, hypoxia decreased (P < 0.05) arterial O2 saturation (%SpO2) at rest (-22%) and during exercise (-28%). Furthermore, VO2max (-39%), HRmax (HR, -8%), maximal pulmonary ventilation (VEmax, -11%), and urinary norepinephrine excretion (-31%) were reduced (P < 0.05) whereas HR at rest (25%) and during EXSUB (16%) and VE at rest (38%) and during EXSUB (70%) were increased (P < 0.05). However, hypoxia-induced changes (Δ) were not randomly distributed between subjects. Between-pair variance was substantially larger than within-pair variance (P < 0.05) for Δ%SpO2 at rest (approximately threefold) and during exercise (approximately fourfold), ΔVO2max (approximately fourfold), ΔHR during exercise (approximately seven- to eightfold), hypoxic ventilatory response (approximately sixfold), and Δ urinary norepinephrine output (approximately threefold). Incidence of acute mountain sickness (AMS) also yielded significant twin similarity (P < 0.05). AMS+ subjects showed approximately 50% greater drop in urinary norepinephrine and lower hypoxic ventilator response than AMS- individuals. Conclusions: Our data suggest that genetic factors regulate cardiorespiratory responses, exercise tolerance, and pathogenesis of AMS symptoms in acute severe hypoxia. Hypoxia-induced sympathetic downregulation was associated with AMS. Copyright © 2014 by the American College of Sports Medicine.


Masschelein E.,Catholic University of Leuven | Van Thienen R.,Catholic University of Leuven | D'Hulst G.,Catholic University of Leuven | Hespel P.,Catholic University of Leuven | And 2 more authors.
FASEB Journal | Year: 2014

Hypoxia-induced muscle wasting is a phenomenon often described with prolonged stays at high altitude, which has been attributed to altered protein metabolism. We hypothesized that acute normobaric hypoxia would induce a negative net protein balance by repressing anabolic and activating proteolytic signaling pathways at rest and postexercise and that those changes could be partially genetically determined. Eleven monozygotic twins participated in an experimental trial in normoxia and hypoxia (10.7% O2). Muscle biopsy samples were obtained before and after a 20-min moderate cycling exercise. In hypoxia at rest, autophagic flux was increased, as indicated by an increased microtubule-associated protein 1 light chain 3 type II/I (LC3-II/I) ratio (+25%) and LC3-II expression (+60%) and decreased p62/SQSTM1 expression (-25%; P<0.05), whereas exercise reversed those changes to a level similar to that with normoxia except for p62/SQSTM1, which was further decreased (P<0.05). Hypoxia also increased Bnip3 (+34%) and MAFbx (+18%) mRNA levels as well as REDD1 expression (+439%) and AMP-activated protein kinase phosphorylation (+22%; P<0.05). Among the molecular responses to hypoxia and/or exercise, high monozygotic similarity was found for REDD1, LC3-II, and LC3-II/I (P<0.05). Our results indicate that environmental hypoxia modulates protein metabolism at rest and after moderate exercise by primarily increasing markers of protein breakdown and, more specifically, markers of the autophagy-lysosomal system, with a modest genetic contribution. © FASEB.


PubMed | Sports and Health Research Group
Type: Journal Article | Journal: Age (Dordrecht, Netherlands) | Year: 2016

Aging is a complex process that is accompanied with changes in both muscle mass and muscle function (strength and performance). Therefore, the current longitudinal study aimed to provide a better insight in 10-year aging-related changes in whole-body muscle mass and strength performance of the leg extensors during the adult life span. Data were gathered within the framework of the first- (2002-2004: baseline) and third-generation Flemish Policy Research Center Sport (2012-2014: follow-up). Results are based on muscle characteristics data of 591 Flemish Caucasian adults (19-73years, 381 men). Skeletal muscle mass (SMM) was determined with bioelectrical impedance analysis. Biodex Medical System 3 dynamometer was used to measure isometric (PTstatic120) and isokinetic (PTdynamic60 and PTdynamic240) strength, ballistic movement speed (S 20%), and muscular endurance (work) of the knee extensors. Overall strength performance was higher at both evaluation moments in men compared to women (p<0.01). But only S 20% declined significantly faster in men compared to women (p<0.01). Age and baseline strength performance were negatively related with the change in strength performance, even when corrected for SMM, protein intake, and energy expenditure during sports (E sport). In conclusion, strength performance was not associated with E sport in this study, but protein intake was associated with isometric strength in men, and with ballistic and isokinetic strength in women. Changes in S 20% were significantly greater in men compared to women. Baseline values of strength performance and age were associated with changes in strength performance parameters, even after correction for SMM, protein intake, and E sport.

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