Extracellular flux analyses reveal differences in mitochondrial PBMC metabolism between high-fit and low-fit females

Analyzing metabolism of peripheral blood mononuclear cells (PBMCs) can possibly serve as a cellular metabolic read-out for lifestyle factors and lifestyle interventions. However, the impact of PBMC composition on PBMC metabolism is not yet clear, neither is the differential impact of a longer-term lifestyle factor versus a short-term lifestyle intervention. We investigated the effect of aerobic fitness level and a recent exercise bout on PBMC metabolism in females. PBMCs from 31 young female adults divided into a high-fit (V̇O2peak ≥ 47 mL/kg/min, N = 15) and low-fit (V̇O2peak ≤ 37 mL/kg/min, N = 16) group were isolated at baseline and overnight after a single bout of exercise (60 minutes, 70% V̇O2peak). Oxygen consumption rate (OCR) and glycolytic rate (GR) were measured using extracellular flux (XF) assays and PBMC subsets were characterized using fluorescence-activated cell sorting (FACS). Basal OCR, FCCP-induced OCR, spare respiratory capacity, ATP-linked OCR, and proton leak were significantly higher in high-fit compared to low-fit females (all P < 0.01), while no significant differences in glycolytic rate (GR) were found (all P > 0.05). A recent exercise bout did not significantly affect GR or OCR parameters (all P > 0.05). The overall PBMC composition was similar between high-fit and low-fit females. Mitochondrial PBMC function was significantly higher in PBMCs from high-fit compared to low-fit females, which was unrelated to PBMC composition and not impacted by a recent bout of exercise. Our study reveals a link between PBMC metabolism and levels of aerobic fitness, increasing the relevance of PBMC metabolism as a marker to study the impact of lifestyle factors on human health.

Effect of an Exercise Bout Prior to the Booster Dose of an Inactivated SARS-CoV-2 Vaccine on Immunogenicity in Immunocompromised Patients

This study aimed to investigate whether a single bout of exercise prior to the homologous booster dose of a SARS-CoV-2 inactivated vaccine (Sinovac-CoronaVac) could enhance immunogenicity in patients with dysfunctional immune system. This was a randomized controlled trial (1:1) within a single-arm, phase 4 vaccination trial, conducted in São Paulo, Brazil. Patients with spondyloarthritis assigned to the intervention group performed an exercise bout comprising three unilateral strength exercises involving eccentric and concentric contractions. After exercising, patients remained at rest for 1 h prior to vaccination, which was applied to the exercised arm. The control group remained at rest before vaccination. Immunogenicity was assessed before (Pre) and one month after (Post) the booster dose using seropositivity rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), frequency of NAb positivity, and NAb activity. Before the booster dose, 16 patients from the exercise group and 16 patients from the control group exhibited seropositivity for IgG (59% vs. 57.1%), one month after the booster dose, seropositivity occurred in 96% vs. 100% of the cases (p = 0.84, group by time interaction). Only 10 patients from the exercise group and 12 patients from the control group showed positive NAb serology at Pre (37% vs. 42.8%). One month following the booster, NAb positivity was 96% vs. 93% (p = 0.41, group-by-time interaction). GMT was comparable between groups at Pre (p > 0.05). At Post, GMT increased similarly in both groups (exercise: 56.9%; control: 57.9%), with no group-by-time interaction (p = 0.82; estimated mean difference between groups at Post [EMD]: -40.4 UA/mL, 95%CI: -327, 246 UA/mL). Likewise, NAb activity was similar between groups at Pre and increased similarly in both of them as a result of the booster (47.5% vs. 39.9%), with no group-by-time interaction (p = 0.99; EMD: -6.19%, 95%CI: -17; 4.6%). In conclusion, a single bout of exercise did not enhance immunogenicity to a homologous booster dose of an inactivated SARS-CoV-2 vaccine among patients with spondyloarthritis. Studies assessing exercise as an adjuvant to first or second doses remain necessary.

Exercise Reduces the Protein Abundance of TXNIP and Its Interacting Partner REDD1 in Skeletal Muscle: Potential Role for a PKA-Mediated Mechanism

Thioredoxin-interacting protein (TXNIP) negatively effects the redox state and growth signaling via its interactions with thioredoxin (TRX) and regulated in development and DNA damage response 1 (REDD1), respectively. TXNIP expression is downregulated by pathways activated during aerobic exercise (AE), via posttranslational modifications (PTMs; serine phosphorylation and ubiquitination). The purpose of this investigation was to determine the effects of acute AE on TXNIP expression, posttranslational modifications, and its interacting partners, REDD1 and TRX. Fifteen healthy adults performed 30 minutes of aerobic exercise (80% VO2max) with muscle biopsies taken before, immediately following, and three hours following the exercise bout. To explore potential mechanisms underlying our in vivo findings, primary human myotubes were exposed to two models of exercise, electrical pulse stimulation (EPS) and palmitate-forskolin-ionomycin (PFI). Immediately following exercise, TXNIP protein decreased, but returned to pre-exercise levels three hours post exercise. These results were replicated in our PFI exercise model only. Although not statistically significant, there was a trending main effect in serine-phosphorylation status of TXNIP (p=0.07) immediately following exercise. REDD1 protein decreased three hours after exercise. AE had no effect on TRX protein expression, gene expression or the activity of its reducing enzyme, thioredoxin reductase. Consequently, AE had no effect on the TRX: TXNIP interaction. Our results indicate that AE leads to acute reductions in TXNIP and REDD1 protein expression. However, these changes did not result in alterations in the TRX: TXNIP interaction and could not be entirely explained by alterations in TXNIP PTMs or changes in TRX expression or activity.

Effects of an acute exercise bout in hypoxia on extracellular vesicle release in healthy and prediabetic subjects

Purpose: To investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Methods: Seventeen healthy (BMI: 23.5±0.5kg·m-2) and fifteen prediabetic (BMI: 27.3±1.2kg·m-2) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia (FiO2 14.0%). Venous blood samples were taken before (T0), during (T30) and after (T60) exercise and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. Results: In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81 and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX and CD9 were upregulated in skeletal muscle after exercise in normoxia; whereas, CD9 and CD81 were downregulated in hypoxia. Conclusions: ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.

Repetitions of Strenuous Exercise Consistently Increase Paraoxonase 1 Concentration and Activity in Plasma of Average-Trained Men

Objectives. Oxidative stress, induced by physical activity, may stimulate the expression, release, and activity of certain antioxidant enzymes. We investigated the effect of three repeated bouts of strenuous exercise on paraoxonase 1 concentration (PON1c) and paraoxonase activity (PON). Methods. Eleven average-trained healthy men (age 34.0 ± 5.2 years) performed three strenuous exercise tests on a treadmill separated by 72 hours periods of resting. PON1c, PON, ferric-reducing activity of plasma (FRAP), lipid profile, C-reactive protein concentration (CRP), and lactate concentration were determined in plasma. Results. Each exercise bout resulted in similar PON1c, PON, FRAP, and high-density lipoprotein concentration (HDL-C) increments, while PON/HDL-C ratio remained stable in all repetitions. Percentage increments at the bout of each exercise were higher for PON1c (by 64.82% at the first, by 92.9% at the second, and by 77.02% at the third exercise) than for PON (by 6.49% at the first, 10.06% at the second, and by 12.32% at the third exercise). Association was found between preexercise PON and PON1c ( r = 0.56 , p = 0.029 ), pre- ( r = 0.87 , p = 0.00003 ) and postexercise HDL-C ( r = 0.6 , p = 0.0002 ), preexercise PON and cardiovascular fitness level of participants measured as VO2max ( r = 0.39 , p = 0.026 ), and postexercise PON and lactate concentration ( r = 0.44 , p = 0.01 ). Conclusions. PON1c and PON increase during strenuous exercise, yet the effect of exercise on PON1 concentration is more pronounced. PON1 does not show tolerance to physical activity. The enzyme may provide short-term protection from oxidative stress in each exercise bout. PON may depend on exercise load. Cardiovascular fitness levels may be associated with PON1 activity.

The Effect of a Single Bout of Exercise on Vitamin B2 Status Is Not Different between High- and Low-Fit Females

High-fitness individuals have been suggested to be at risk of a poor vitamin B2 (riboflavin) status due to a potentially higher vitamin B2 demand, as measured by the erythrocyte glutathione reductase (EGR) activation coefficient (EGRAC). Longer-term exercise interventions have been shown to result in a lower vitamin B2 status, but studies are contradictory. Short-term exercise effects potentially contribute to discrepancies between studies but have only been tested in limited study populations. This study investigated if vitamin B2 status, measured by EGRAC, is affected by a single exercise bout in females who differ in fitness levels, and that represents long-term physical activity. At baseline and overnight after a 60-min cycling bout at 70% V·O2peak, EGR activity and EGRAC were measured in 31 young female adults, divided into a high-fit (V·O2peak ≥ 47 mL/kg/min, N = 15) and low-fit (V·O2peak ≤ 37 mL/kg/min, N = 16) group. A single exercise bout significantly increased EGR activity in high-fit and low-fit females (Ptime = 0.006). This response was not affected by fitness level (Ptime*group = 0.256). The effect of exercise on EGRAC was not significant (Ptime = 0.079) and not influenced by EGR activity. The exercise response of EGRAC was not significantly different between high-fit and low-fit females (Ptime*group = 0.141). Thus, a single exercise bout increased EGR activity, but did not affect EGRAC, indicating that vitamin B2 status was not affected. The exercise response on EGRAC and EGR did not differ between high-fit and low-fit females.

Acute Aerobic Exercise Induces Short-Term Reductions in Ambulatory Blood Pressure in Patients With Hypertension: A Systematic Review and Meta-Analysis

Chronic exercise reduces clinic and ambulatory blood pressure (BP), but the short-term effects of an acute exercise bout on ambulatory BP have not been studied widely. We reviewed the literature regarding the short-term effects of acute exercise on ambulatory BP in patients with hypertension and considered moderating factors (medication status and exercise modality/intensity) on ambulatory BP outcomes. A systematic search was conducted (PubMed, Cochrane Library, and Scopus; since inception to January 1, 2021) for crossover randomized controlled trials assessing the short-term effects of acute exercise on ambulatory BP in hypertensive individuals versus nonexercise control conditions. A meta-analysis was conducted for 24-hour, daytime, and nighttime systolic and diastolic BP. Subanalyses also were performed attending to medication status and exercise modality/intensity. Thirty-seven studies (N=822) met the inclusion criteria. A single acute exercise bout reduces 24-hour (systolic BP, −1.6 mm Hg [95% CI, −2.4 to −0.8] for all exercise modalities combined; diastolic BP, −1.0 mm Hg [95% CI, −1.5 to −0.5]), daytime (−3.1 mm Hg [95% CI, −4.1 to −2.2]; -2.0 mm Hg [95% CI, −2.8 to −1.2]), and nighttime ambulatory BP (−1.8 mm Hg [95% CI, −3.0 to −0.6]; −1.5 mm Hg [95% CI, −2.3 to −0.6]), respectively. The magnitude of the effect appears similar in medicated and nonmedicated patients. In separate analyses for exercise modalities, aerobic exercises reduce all ambulatory BP measures ( P <0.001) yet with no significant effects for resistance or combined (aerobic and resistance) exercise for any ambulatory BP measure. Vigorous aerobic exercise tends to produce the largest effects. A single bout of acute aerobic exercise, reduces ambulatory BP over 24 hours in medicated and nonmedicated hypertensive adults.

Normalization of global longitudinal strain after a 30-seconds exercise bout in elite athletes

Background/Introduction Transthoracic echocardiography (TTE) is often the first diagnostic imaging modality of choice in athlete care to differentiate between physiological adaptation to sports and pathology. Mechanical strain as outcome measure, i.e. left ventricular (LV) global longitudinal strain (GLS), has been suggested as a tool to detect early signs of myocardial diseases in athletes. However, low or very low rates of myocardial deformation can also be associated with cardiac adaptation to sports. We hypothesize that observing decreased cardiac deformation in elite athletes may be a sign of an outspoken relaxed cardiac state, rather than pathology. Therefore, we investigated whether a short exercise bout can normalize strain values in elite athletes with abnormal resting GLS. Methods We prospectively enrolled elite athletes who participated in the ELITE (Evaluation of Lifetime Participation in Intensive Top-level Sports and Exercise) cohort. In short, ELITE is a prospective athlete cohort, which collects medical history, ECG, TTE and cardiac magnetic resonance (CMR) data in elite athletes (Olympic/Paralympic level or comparable). For this analysis, we analysed TTEs of asymptomatic athletes without cardiovascular disease and with a structurally normal heart on CMR. TTE (Vivid, GE) was performed in each athlete according to guidelines at rest. After a short exercise bout, consisting of 20 squats, additional measurements were performed when heart-rate (HR) was comparable to HR during pre-exercise measurements. TTE data was assessed using EchoPAC (GE). Paired t-tests were calculated for functional parameters; boxplots for pre- and post-exercise measurements; and GLS delta (pre- to post-exercise) for each athlete was calculated were plotted; using R. GLS ≥−16% was considered decreased and −16% ≥ GLS &gt;−18% borderline. Results Our population comprised 51 athletes (35% women), with a mean age (±SD) of 26.4±5.2 years, and mean BSA of 2±0.3m2. Athletic disciplines consisted of road cycling (n=25), hockey (n=7), swimming (n=5), and 7 miscellaneous sports (n=14). We observed an increase of myocardial deformation after a short bout of exercise: mean GLS delta of 2.6±2% (pre- vs post-exercise GLS: −18.2±2.1% vs −20.8±1.9%; P≤0.001; Figure, A). Furthermore, mean LV stroke volumes were 94±19ml vs 103±23ml (P=0.020), ejection fractions (EF) 57±4% vs 60±4% (P≤0.001), and HR 55±10bpm vs 54±13bpm (P=0.8). Finally, we found a decreased strain in 8 athletes (16%), in 7 of which increased to normal values. Mean delta GLS was 4.5±2.2 (pre- vs post-exercise GLS: −14.9±1.1% vs −19.4±2.7%, P=0.002, Figure, B). The athlete who did not show an increase to normal GLS levels had a decreased LV EF (42%), but showed no other signs of cardiac pathology (MRI, biomarkers, complaints). Conclusion In athletes with abnormal GLS at rest, performing a short exercise bout may provide a pragmatic method to separate decreased GLS due to true pathology from sports adaptation. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Amsterdam Movement Sciences