Accumulation and nuclear import of HIF1 alpha during high and low oxygen concentration in skeletal muscle cells in primary culture

AbstractThe hypoxia-inducible-factor-1 (HIF1) mediates the transcriptional upregulation of several target genes during hypoxia. HIF1 itself is known to be regulated essentially by ubiquitinylation and proteolytic degradation of the subunit HIF1α of the dimeric transcription factor HIF1. In contrast to other tissues, skeletal muscle expresses high amounts of HIF1α in normoxia as well as in hypoxia. In view of this, we aimed to investigate HIF1α accumulation and subcellular localization as well as the transcriptional activity of the HIF1α-regulated gene of glyceraldehyde dehydrogenase (GAPDH) in skeletal muscle cells exposed to low oxygen concentration (3% O2), normoxia (20% O2) or high oxygen concentration (42% O2). Immunofluorescence analysis reveals that under normoxic and high oxygen conditions, significant amounts of HIF1α can be found exclusively in the cytoplasm of the myotubes. Muscle cells treated with CoCl2, a known inhibitor of HIF1α degradation, show even higher levels of HIF1α, again exclusively in the cytoplasm. Under conditions of low oxygen, HIF1α in controls as well as in CoCl2-treated cells is found in the nuclei. CdCl2 inhibits nuclear import of HIF1α at low oxygen concentration and leads to a transcriptional downregulation of the marker enzyme of anaerobic glycolysis GAPDH. Immunoprecipitation with anti-HIF1α antibody co-precipitates HSP90 in an oxygen-dependent manner, more at high pO2 than at low pO2. Cadmium-treated samples also show high amounts of co-immunoprecipitated HSP90, independent of oxygen concentration. We conclude that in skeletal muscle cells, HIF1α, in contrast to other tissues, may, in addition to its regulation by degradation, also be regulated by binding to HSP90 and subsequent inhibition of its import into the nuclei

Heterogeneous effects of eccentric training and nordic hamstring exercise on the biceps femoris fascicle length based on ultrasound assessment and extrapolation methods: A systematic review of randomised controlled trials with meta-analyses

Objective To systematically review the effects of eccentric training based on biceps femoris fascicle length using ultrasound assessment and extrapolation methods. Design Systematic review and meta-analysis of randomised controlled trials. Data sources CENTRAL, CINAHL Plus with full text, PubMed and OpenGrey databases were searched on 6 July 2021. Eligibility criteria for selecting studies Randomised controlled trials (RCTs) lasting at least four weeks and presenting data about biceps femoris (BF) fascicle length (FL) as an outcome. Method Searching databases, screening studies, performing risk of bias assessments and determining the level of evidence (LoE) for each meta-analysis were applied during the study. PRISMA 2020 statement and Cochrane Handbook for Systematic Reviews of Interventions were used as the guidelines of this systematic review. Results Eight randomised controlled trials included in meta-analyses. Based on the very low and low LoE, eccentric training has small (g = 0.29, 95% CI [-0.26, 0.85]), moderate (g = 0.72, 95% CI [0.17, 1.28]) and large (g = 2.20, 95% CI [0.99, 3.41]) effect sizes (ES) based on manual linear extrapolation (MLE), panoramic ultrasound scanning and trigonometric equation methods, respectively. Similarly, Nordic hamstring exercise (NHE) has small (g = 0.23 [-1.02, 1.47]), small (g = 0.38, 95% CI [-0.50, 1.27]) and large (g = 1.98, 95% CI [0.52, 3.44]) ES based on the MLE, panoramic ultrasound scanning and trigonometric equation methods, respectively. Conclusion ES of eccentric training, including NHE, vary between the MLE, panoramic ultrasound scanning, and equation methods. The relevant scientific community should have a consensus on measurement standards of the BF FL measurements. Further studies can be conducted to compare the effects of eccentric training based on the ultrasound assessment and extrapolation methods

The Effects of Resistance Training on Architecture and Volume of the Upper Extremity Muscles: A Systematic Review of Randomised Controlled Trials and Meta-Analyses

To systematically review the effects of exercise on fascicle geometry and muscle size parameters of the upper extremity muscles, the CENTRAL, CINAHL, PubMed and OpenGrey databases were searched on 31 July 2021. Finally, 17 randomised controlled trials (RCTs) were included in this systematic review. High-intensity bench press training (g = 1.03) and 12 RM bench press exercises (g = 1.21) showed a large effect size on increasing pectoralis major muscle size. In the elbow extensors, large effects were reported for an increase in muscle size with isometric maximal voluntary co-contraction training (g = 1.97), lying triceps extension exercise (g = 1.25), and nonlinear periodised resistance training (g = 2.07). In addition, further large effects were achieved in the elbow flexors via traditional elbow flexion exercises (g = 0.93), concentric low-load forearm flexion-extension training (g = 0.94, g = 1), isometric maximal voluntary co-contraction training (g = 1.01), concentric low-load forearm flexion-extension training with blood flow restriction (g = 1.02, g = 1.07), and nonlinear periodised resistance training (g = 1.13, g = 1.34). Regarding the forearm muscles, isometric ulnar deviation training showed a large effect (g = 2.22) on increasing the flexor carpi ulnaris and radialis muscle size. Results show that these training modalities are suitable for gaining hypertrophy in the relevant muscles with at least four weeks of training duration. Future RCTs should investigate the effects of exercise modalities on the triceps brachii fascicle geometry, the infraspinatus muscle thickness (MT) and the subscapular MT due to their associations with sports performance

The Effects of Beetroot Juice on Blood Pressure, Microvascular Function and Large-Vessel Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Pilot Study in Healthy Older Adults.

Dietary nitrate (NO ) has been reported to improve endothelial function (EF) and blood pressure (BP). However, most studies only assess large-vessel EF with little research on the microvasculature. Thus, the aim of the present pilot study is to examine NO supplementation on microvascular and large-vessel EF and BP. Twenty older adults (63 ± 6 years) were randomized to a beetroot juice (BRJ) or placebo (PLA) group for 28 (±7) days and attended three laboratory visitations. Across visitations, blood pressure, microvascular function and large-vessel EF were assessed by laser Doppler imaging (LDI) with iontophoresis of vasoactive substances and flow-mediated dilatation (FMD), respectively. Plasma NO concentrations, BP and the presence of NO reducing bacteria were also assessed. Plasma NO increased following two weeks of BRJ supplementation (p = 0.04) along with a concomitant decrease in systolic and diastolic BP of approximately −6 mmHg and −4 mmHg, respectively (p = 0.04; p = 0.01, respectively). BP remained unchanged in the PLA group. There were no significant differences in endothelium-dependent or endothelium-independent microvascular responses between groups. FMD increased by 1.5% following two weeks of BRJ (p = 0.04), with only a minimal (0.1%) change for the PLA group. In conclusion, this pilot study demonstrated that medium-term BRJ ingestion potentially improves SBP, DBP and large-vessel EF in healthy older adults. The improvements observed in the present study are likely to be greater in populations presenting with endothelial dysfunction. Thus, further prospective studies are warranted in individuals at greater risk for cardiovascular disease

Differential effects of repeated inspiratory and limb muscle loading on effort perception in patients with obstructive sleep apnea and healthy males

Abstract Obstructive sleep apnea (OSA) is characterized by collapse of the upper airways during sleep. The contribution of alterations in effort perception is not understood. This study investigated the response of inspiratory and quadriceps muscles to repetitive loading on effort perception in OSA patients, pre and post continuous positive airway pressure (CPAP) treatment, and in healthy individuals. Twenty‐one OSA patients and 40 healthy participants completed protocols for repetitive inspiratory and leg muscle loading combined with intermittent rating of perceived exertion (RPE 14—somewhat hard/hard) to assess effort sensitivity. Electromyography, inspiratory pressure and isometric force were measured. OSA patients reported higher fatiguability of respiratory and leg muscles than controls. OSA patients revealed lower effort sensitivity in the leg muscles compared with controls, while repetitive loading led to a decline in force production. In the respiratory system, OSA patients revealed similar effort sensitivity at baseline compared with controls, but a large reduction in effort sensitivity after loading. Baseline effort sensitivity was correlated with apnea‐hypopnea index (AHI). After CPAP treatment, OSA patients revealed a decreased baseline effort sensitivity with a missing loading response. Effort sensitivity was differentially affected in the respiratory and leg systems with outcomes of CPAP treatment suggesting a full reversibility. Outcomes suggest that reversible adaptive response of effort perception in the respiratory system might contribute to the severity of OSA

Alterations in biceps femoris long head fascicle length, eccentric hamstring strength qualities and single-leg hop distance throughout the ninety minutes of TSAFT90 simulated football match

IntroductionFootball matches show higher hamstring strain injuries (HSIs) than football training. The occurrence of HSIs increases in the last fifteen minutes of both halves of football matches and shows an incremental trend towards the end of the ninety minutes.ObjectivesThis study aimed to examine football-specific fatigue-induced alterations in risk factors of the HSIs, including biceps femoris long head fascicle length via ultrasonography (BFlh FL), single-leg hop distance, hamstrings' maximal eccentric strength, and single-leg hamstring bridge test (SLHB) performance.MethodologyDuring ninety minutes of the TSAFT90 football simulation, the BFlh FL and single-leg hop distance were measured three times (before, at half-time and after 90 minutes of simulated match-play), and maximal hamstrings eccentric strength and SLHB test scores were recorded twice (before and after simulated match-play) for both legs in physically active participants (n = 15).ResultsMaximal eccentric hamstrings' strength (dominant leg (D): p ConclusionsMaximal eccentric strength and the SLHB performance of hamstrings are reduced after 90 minutes of simulated football match-play. Practitioners may consider focusing on improving eccentric strength and the SLHB performance. Future studies should examine alterations in the BFlh fascicles' dynamic lengthening and shortening ability during a football match

Ecological momentary assessment of food perceptions and eating behavior using a novel phone application in adults with or without obesity

We developed a smart phone application to measure participants’ food-reward perceptions and eating behavior in their naturalistic environment. Intensity ratings (0 - not at all to 10 - very strongly) of perceived anticipation of food (wanting) and food enjoyment at endpoint of intake (liking) were recorded as they occurred over a period of 14 days. Moreover, food craving trait, implicit and explicit attitude towards healthy food, and body composition were assessed. 53 participants provided complete data. Participants were classified by percentage of body fat; 33 participants with lower body fat (L-group) and 20 with higher body fat (H-group; ≥25% body fat for males and ≥32% for females). L-group participants reported 6.34 (2.00) food wanting events per day, whereas H-group participants recorded significantly fewer food wanting events (5.07 (1.42)); both groups resisted about the same percentage of wanting events (L-group: 29.2 (15.5)%; H-group 27.3 (12.8)%). Perceived intensity ratings were significantly different within the L-group in the order liking (7.65 (0.81)) > un-resisted wanting (leading to eating) (7.00 (1.01)) > resisted wanting (not leading to eating) (6.02 (1.72)) but not in the H-group. Liking scores (L-group: 7.65 (0.81); H-group: 7.14 (1.04)) were significantly higher in L-group than in H-group after controlling for age. Our results show that individuals with higher percentage of body fat show less food enjoyment after intake and reveal no differentiation in intensity ratings of perceived anticipatory and consummatory food reward. These results are consistent with a hypothesized reward deficiency among individuals with higher percentage of body fat