Adaptation To Exercise Research Articles

Improved Tricuspid Valve Function, Preload Recruitment and Ventricular Efficiency During Submaximal Exercise in Patients with Unoperated Ebstein's Anomaly: An MRI Study.

Adolescents and adults with native Ebstein's anomaly (EA) are at the benign part of the Ebstein spectrum, having survived infancy without surgery. In this population, surgical indication and timing remain objects of controversy and depend, among other factors, on exercise capacity. To better understand the pathophysiology of exercise adaptation in native EA. Retrospective. Ten patients with unoperated EA (age range 18-61 years) and 13 healthy subjects as controls. Balanced steady-state free precession cine and phase contrast flow sequences at 1.5 T. We measured volumes and flows at rest and during submaximal exercise. Hemodynamic parameters including stroke volume (SV), cardiac index (CI), ejection fraction (EF), and tricuspid regurgitation (TR) were calculated. We used nonparametric Mann-Whitney U-test and Wilcoxon signed-rank test. A P-value of <0.05 was considered statistically significant. Rest CI and SV were significantly higher in controls; rest heart rate (HR) was similar in the two groups (median 71 bpm by patients and 65 bpm by controls, P=0.448). During exercise, CI increased significantly in both groups: from 2.40 to 3.35 L/min/m2 in the patient group and from 3.60 to 4.20 L/min/m2 in controls; HR increased significantly in both groups. SV increased significantly in the patient group, whereas it remained stable in controls (P=0.5284). Patients' median TR decreased significantly: median 42% at rest and 30% during exercise; concomitantly, left ventricular (LV) preload increased significantly (+3% indexed LV end-diastolic volume) as did LVEF (median 59% at rest vs. 65% during exercise). During submaximal exercise, patients with mild to moderate EA improved their cardiovascular system's total efficiency by increasing CI; this was obtained by an increase in HR and by the recruitment of volume, as shown by an increased LV end-diastolic volume and SV, with simultaneous decrease in TR. This was different from healthy subjects in which CI increased only due to HR increase. 3 TECHNICAL EFFICACY STAGE: 3.

Plasma-Derived microRNAs Are Influenced by Acute and Chronic Exercise in Patients With Heart Failure With Reduced Ejection Fraction.

Background: Exercise training improves VO2peak in heart failure with reduced ejection fraction (HFrEF), but the effect is highly variable as it is dependent on peripheral adaptations. We evaluated changes in plasma-derived miRNAs by acute and chronic exercise to investigate whether these can mechanistically be involved in the variability of exercise-induced adaptations.Methods: Twenty-five male HFrEF patients (left ventricular ejection fraction < 40%, New York Heart Association class ≥ II) participated in a 15-week combined strength and aerobic training program. The effect of training on plasma miRNA levels was compared to 21 male age-matched sedentary HFrEF controls. Additionally, the effect of a single acute exercise bout on plasma miRNA levels was assessed. Levels of 5 miRNAs involved in pathways relevant for exercise adaptation (miR-23a, miR-140, miR-146a, miR-191, and miR-210) were quantified using RT-qPCR and correlated with cardiopulmonary exercise test (CPET), echocardiographic, vascular function, and muscle strength variables.Results: Expression levels of miR-146a decreased with training compared to controls. Acute exercise resulted in a decrease in miR-191 before, but not after training. Baseline miR-23a predicted change in VO2peak independent of age and left ventricular ejection fraction (LVEF). Baseline miR-140 was independently correlated with change in load at the respiratory compensation point and change in body mass index, and baseline miR-146a with change in left ventricular mass index.Conclusion: Plasma-derived miRNAs may reflect the underlying mechanisms of exercise-induced adaptation. In HFrEF patients, baseline miR-23a predicted VO2peak response to training. Several miRNAs were influenced by acute or repeated exercise. These findings warrant exploration in larger patient populations and further mechanistic in vitro studies on their molecular involvement.

Exercise adaptations and TGF-β1 levels in recreational cyclists

BackgroundCycling is a physical exercise that is widely performed to improve physical fitness. Regular physical exercise will lead to adaptations to exercise. This adaptation is useful in suppressing the production of reactive oxygen stress (ROS) generated in response to cellular metabolism that uses oxygen. Transforming growth factor beta-1 (TGF-β1) plays a role in increasing the production of ROS, thus, when the concentration is low, it would lead to an improvement in physical fitness. This study aims to compare levels of TGF-β1 between recreational cyclists and sedentary groups. In addition, this research also compares several other parameters, which are fasting blood sugar levels and lipid profiles (triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol) between cyclists and sedentaries. MethodsThis was an observational analytical study with a cross-sectional design. The research subjects consisted of 2 groups, each consisting of 21 participants, namely the recreational cyclist and the sedentary group. Anthropometric examinations were carried out, including body weight, height, body mass index, waist circumference, and body fat percentage. Fasting blood glucose concentration and lipid profile (Triglyceride – TG, Total Cholesterol – Total C, HDL Cholesterol – HDL-C, and LDL Cholesterol – LDL-C) were determined by the enzymatic colorimetric methods, and TGF-β1 levels were determined using the fluorescence of specific antibodies for TGF-β1 (pg/ml) using ELISA method. Statistical analysis was performed using IBM SPSS v. 25. ResultsThe anthropometric variables, other than body height, did not differ significantly between the two groups, so did the fasting blood glucose concentration. Nevertheless, the lipid profile (TG, Total C, HDL-C and LDL-C) were found to be significantly better in the cyclist group (p < 0.05).The mean level of TGF-β1 in recreational cyclists was 8, 908.48 pg/ml, lower than the control group, 10, 229.28 pg/ml. The results of the unpaired t-test showed significant mean differences between the two groups, (p = 0.001; p < 0.05). ConclusionThe levels of TGF-β1 in the recreational cyclist group were lower than the sedentary group. Regular physical exercise will trigger exercise adaptations that can suppress latent TGF-β1 activation.

Exercise and Sestrin Mediate Speed and Lysosomal Activity in Drosophila by Partially Overlapping Mechanisms.

Chronic exercise is widely recognized as an important contributor to healthspan in humans and in diverse animal models. Recently, we have demonstrated that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits in flies and mice. Knockout of Sestrins prevents exercise adaptations to endurance and flight in Drosophila, and similarly prevents benefits to endurance and metabolism in exercising mice. In contrast, overexpression of dSestrin in muscle mimics several of the molecular and physiological adaptations characteristic of endurance exercise. Here, we extend those observations to examine the impact of dSestrin on preserving speed and increasing lysosomal activity. We find that dSestrin is a critical factor driving exercise adaptations to climbing speed, but is not absolutely required for exercise to increase lysosomal activity in Drosophila. The role of Sestrin in increasing speed during chronic exercise requires both the TORC2/AKT axis and the PGC1α homolog spargel, while dSestrin requires interactions with TORC1 to cell-autonomously increase lysosomal activity. These results highlight the conserved role of Sestrins as key factors that drive diverse physiological adaptations conferred by chronic exercise.

Got Beer? A Systematic Review of Beer and Exercise.

Beer is used to socialize postexercise, celebrate sport victory, and commiserate postdefeat. Rich in polyphenols, beer has antioxidant effects when consumed in moderation, but its alcohol content may confer some negative effects. Despite beer's popularity, no review has explored its effects on exercise performance, recovery, and adaptation. Thus, a systematic literature search of three databases (PubMed, SPORTDiscus, and Web of Science) was conducted by two reviewers. The search resulted in 16 studies that were appraised and reviewed. The mean PEDro score was 5.1. When individuals are looking to rehydrate postexercise, a low-alcohol beer (<4%) may be more effective. If choosing a beer higher in alcoholic content (>4%), it is advised to pair this with a nonalcoholic option to limit diuresis, particularly when relatively large volumes of fluid (>700ml) are consumed. Adding Na+ to alcoholic beer may improve rehydration by decreasing fluid losses, but palatability may decrease. These conclusions are largely based on studies that standardized beverage volume, and the results may not apply equally to situations where people ingest fluids and food ad libitum. Ingesting nonalcoholic, polyphenol-rich beer could be an effective strategy for preventing respiratory infections during heavy training. If consumed in moderation, body composition and strength qualities seem largely unaffected by beer. Mixed results that limit sweeping conclusions are owed to variations in study design (i.e.,hydration and exercise protocols). Future research should incorporate exercise protocols with higher ecological validity, recruit more women, prioritize chronic study designs, and use ad libitum fluid replacement protocols for more robust conclusions.

Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus.

Excess nutrient intake and lack of exercise characterize the problem of obesity and are common factors in insulin resistance (IR). With an increasing number of prediabetic, and type 2 diabetic populations, metformin is still the most prescribed glucose-lowering drug and is often accompanied by recommendations for regular physical exercise. Metformin, by the inhibition of complex 1 of the electron transport chain, and exercise, by increasing energy expenditure, both elicit a low cellular energy state that leads to improvements in glucose control via activation of adenosine 5ʹ monophosphate-activated protein kinase (AMPK). An augmented stimulation of the energy-sensing enzyme AMPK by either of the two modalities leads to an increase in glycogenolysis, glucose uptake, fat oxidation, a decrease in glycogen and protein synthesis, and gluconeogenesis in muscle and the liver, which are remarked as having positive effects on metabolic pathophysiology observed in IR and type 2 diabetes mellitus (T2DM). While both modalities exploit the energy-sensing enzyme AMPK to attain glucose homeostasis, the synergistic effect of these two treatments is not distinctly supported by the literature. Further, an antagonistic dynamic has been observed in cases where metformin and exercise were combined. Reduction of insulin-sensitizing effects of exercise and an overall hindrance of exercise performance and adaptations have been reported and could suggest the possible incongruity of these two modalities. The aim of this review is to elucidate the effect that metformin and exercise have on the management of the metabolic abnormalities observed in T2DM and to provide an insight into the interaction of these two modalities.

Co-expression analysis identifies networks of miRNAs implicated in biological ageing and modulated by short-term interval training

Exercise training seems to promote healthy biological ageing partly by inducing telomere maintenance, yet the molecular mechanisms are not fully understood. Recent studies have emphasised the importance of microRNAs (miRNAs) in ageing and their ability to mirror pathophysiological alterations associated with age-related diseases. We examined the association between aerobic fitness and leukocyte telomere length before determining the influence of vigorous exercise training on the regulation of leukocyte miRNA networks. Telomere length was positively correlated to aerobic fitness (r = 0.32, p = 0.02). 104 miRNAs were differentially expressed after six weeks of thrice-weekly sprint interval training (SIT) in healthy men (q < 0.05). Gene co-expression analysis (WGCNA) detected biologically meaningful miRNA networks, five of which were significantly correlated with pre-SIT and post-SIT expression profiles (p < 0.001) and telomere length. Enrichment analysis revealed that the immune response, T cell differentiation and lipid metabolism associated miRNAs clusters were significantly down-regulated after SIT. Using data acquired from the Gene Expression Omnibus (GEO), we also identified two co-expressed miRNAs families that were modulated by exercise training in previous investigations. Collectively, our findings highlight the miRNA networks implicated in exercise adaptations and telomere regulation, and suggest that SIT may attenuate biological ageing through the control of the let-7 and miR-320 miRNA families.

Relationship Between Maximal Fat Oxidation And Ventilatory Threshold In Endurance Trained Males

PURPOSE: Training above ventilatory threshold (VT), and corresponding heart rate, have resulted in improvements in aerobic capacity; the ability to oxidize fatty acids is a limiting factor in endurance performance. Additionally, little is known about the contribution of body composition on maximal fat oxidation (Fatmax). The purpose of this study was to characterize Fatmax and its relationship to VT in endurance trained young adult males. A secondary purpose was to understand the impact of body composition on Fatmax. METHODS: 25 trained males (Age: 22.2 ± 2.4 yrs; Height:177.0 ± 4.8 cm; Weight: 75.3 ± 6.9 kg; VO2max: 50.5 ± 14.6 mL/kg/min) were assessed for body composition using dual-energy X-ray absorptiometry to estimate lean mass (LM), fat mass (FM), and percent body fat (%BF). All subjects performed an incremental graded exercise test to volitional exhaustion. Fatmax was determined as the exercise intensity (%VO2max) at which the highest rate of fat oxidation was observed. VT was determined automatically from the software as the point by which respiration increased to compensate for CO2 and lactate accumulation. Paired t-tests were used to determine the differences between Fatmax and VT%VO2max, FatmaxVO2 and VTVO2, and HR at Fatmax and VT. Multiple linear regression was used to analyze the influence of body composition on Fatmax. RESULTS: There were no significant differences between Fatmax and VT%VO2 (Mean Difference ± Standard Error: -0.2 ± 0.1%; p = 0.107) or FatmaxVO2 and VTVO2 (-3.4 ± 3.1 L/min; p = 0.288). FatmaxHR was significantly lower than VTHR (-11.7 ± 3.1 bpm; p = 0.001). LM, FM, %BF did not significantly influence Fatmax (F = 0.888, R2 = 0.13, p = 0.464). CONCLUSIONS: The similar intensity observed between VT and Fatmax suggests training above VT could be a useful strategy for maximizing fat oxidation during exercise, thereby supporting glycogen sparing in addition to enhanced training volume and exercise adaptations. Body composition does not appear to be an important factor for Fatmax in young males.

Pro-inflammatory Vascular Stress in Spontaneously Hypertensive Rats Associated With High Physical Activity Cannot Be Attenuated by Aldosterone Blockade.

The effect of high physical activity, performed as voluntary running wheel exercise, on inflammation and vascular adaptation may differ between normotensive and spontaneously hypertensive rats (SHRs). We investigated the effects of running wheel activity on leukocyte mobilization, neutrophil migration into the vascular wall (aorta), and transcriptional adaptation of the vascular wall and compared and combined the effects of high physical activity with that of pharmacological treatment (aldosterone antagonist spironolactone). At the start of the 6th week of life, before hypertension became established in SHRs, rats were provided with a running wheel over a period of 10-months'. To investigate to what extent training-induced changes may underlie a possible regression, controls were also generated by removal of the running wheel for the last 4 months. Aldosterone blockade was achieved upon oral administration of Spironolactone in the corresponding treatment groups for the last 4 months. The number of circulating blood cells was quantified by FACS analysis of peripheral blood. mRNA expression of selected proteins was quantified by RT-PCR. Histology and confocal laser microscopy were used to monitor cell migration. Although voluntary running wheel exercise reduced the number of circulating neutrophils in normotensive rats, it rather increased it in SHRs. Furthermore, running wheel activity in SHRs but not normotensive rats increased the number of natural killer (NK)-cells. Except of the increased expression of plasminogen activator inhibitor (PAI)-1 and reduction of von Willebrand factor (vWF), running wheel activity exerted a different transcriptional response in the vascular tissue of normotensive and hypertensive rats, i.e., lack of reduction of the pro-inflammatory IL-6 in vessels from hypertensive rats. Spironolactone reduced the number of neutrophils; however, in co-presence with high physical activity this effect was blunted. In conclusion, although high physical activity has beneficial effects in normotensive rats, this does not predict similar beneficial effects in the concomitant presence of hypertension and care has to be taken on interactions between pharmacological approaches and high physical activity in hypertensives.

Signals from the Circle: Tricarboxylic Acid Cycle Intermediates as Myometabokines

Regular physical activity is an effective strategy to prevent and ameliorate aging-associated diseases. In particular, training increases muscle performance and improves whole-body metabolism. Since exercise affects the whole organism, it has countless health benefits. The systemic effects of exercise can, in part, be explained by communication between the contracting skeletal muscle and other organs and cell types. While small proteins and peptides known as myokines are the most prominent candidates to mediate this tissue cross-talk, recent investigations have paid increasing attention to metabolites. The purpose of this review is to highlight the potential role of tricarboxylic acid (TCA) metabolites as humoral mediators of exercise adaptation processes. We focus on TCA metabolites that are released from human skeletal muscle in response to exercise and provide an overview of their potential auto-, para- or endocrine health-promoting effects.

Adaptations to Post-exercise Cold Water Immersion: Friend, Foe, or Futile?

In the last decade, cold water immersion (CWI) has emerged as one of the most popular post-exercise recovery strategies utilized amongst athletes during training and competition. Following earlier research on the effects of CWI on the recovery of exercise performance and associated mechanisms, the recent focus has been on how CWI might influence adaptations to exercise. This line of enquiry stems from classical work demonstrating improved endurance and mitochondrial development in rodents exposed to repeated cold exposures. Moreover, there was strong rationale that CWI might enhance adaptations to exercise, given the discovery, and central role of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in both cold- and exercise-induced oxidative adaptations. Research on adaptations to post-exercise CWI have generally indicated a mode-dependant effect, where resistance training adaptations were diminished, whilst aerobic exercise performance seems unaffected but demonstrates premise for enhancement. However, the general suitability of CWI as a recovery modality has been the focus of considerable debate, primarily given the dampening effect on hypertrophy gains. In this mini-review, we highlight the key mechanisms surrounding CWI and endurance exercise adaptations, reiterating the potential for CWI to enhance endurance performance, with support from classical and contemporary works. This review also discusses the implications and insights (with regards to endurance and strength adaptations) gathered from recent studies examining the longer-term effects of CWI on training performance and recovery. Lastly, a periodized approach to recovery is proposed, where the use of CWI may be incorporated during competition or intensified training, whilst strategically avoiding periods following training focused on improving muscle strength or hypertrophy.

Interaction Between Non-Insulin Glucose-Lowering Medication and Exercise in Type 2 Diabetes Mellitus - New Findings on SGLT2 Inhibitors.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which block glucose reabsorption in the kidneys, represent a novel class of non-insulin glucose-lowering medication used in the pharmacological therapy of type 2 diabetes mellitus (T2DM). They became available after the introduction of incretin-based therapies with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or dipeptidyl peptidase-4 (DPP4) inhibitors (1). All these newer drugs have multiple effects that go beyond their glucose-lowering effect (2). It has been concluded in a meta-analysis that patients with T2DM who take SGLT2 inhibitors experience fewer major adverse cardiovascular events and show reduced all-cause mortality (3). Another meta-analysis (including data from patients with T2DM, heart failure or chronic kidney disease) demonstrates that SGLT2 inhibitor use can reduce the risk of cardiac arrhythmia (4). Yet another meta-analysis shows that SGLT2 inhibitor use can reduce blood pressure in T2DM patients (5). The beneficial effects of SGLT2 inhibitors on the cardiovascular system do not only depend on the glucose-lowering effect, but are also based on other possible mechanisms, e.g. increased natriuresis and diuresis [for an overview, see (6)]. Although it is generally accepted that regular exercise also has glucose-lowering and beneficial cardiovascular effects, the combination of non-insulin glucose-lowering medication and regular exercise does not necessarily have to have additive effects on glycemic variables and/or cardiovascular health/cardiorespiratory fitness. By contrast, it has been concluded in some studies involving insulin resistant patients who take metformin, which is often recommended as the first-line medication in T2DM, that certain exercise adaptations (improvements in insulin sensitivity, peak oxygen uptake, blood pressure, lipid profile) are not further increased or can even be attenuated through metformin use (7–11). Details on the underlying molecular mechanisms of how metformin and exercise interact and affect exercise training outcomes have yet to be determined. Among others, changes in (exercise-induced) oxidative stress and/or inflammation (with effects on post-exercise cellular signals) or in (exercise-induced) autophagy have been discussed (10, 12). It should be noted, however, that not all studies report similar or blunted adaptations for all outcomes when exercise training is combined with metformin use. In the study of Viskochil et al. (13), for example, metformin and exercise training, but not exercise alone, lowered proinsulin concentrations and increased insulin clearance in adults with prediabetes. But what about the influence of SGLT2 inhibitors on training outcomes?

Time trajectories in the transcriptomic response to exercise - a meta-analysis

Exercise training prevents multiple diseases, yet the molecular mechanisms that drive exercise adaptation are incompletely understood. To address this, we create a computational framework comprising data from skeletal muscle or blood from 43 studies, including 739 individuals before and after exercise or training. Using linear mixed effects meta-regression, we detect specific time patterns and regulatory modulators of the exercise response. Acute and long-term responses are transcriptionally distinct and we identify SMAD3 as a central regulator of the exercise response. Exercise induces a more pronounced inflammatory response in skeletal muscle of older individuals and our models reveal multiple sex-associated responses. We validate seven of our top genes in a separate human cohort. In this work, we provide a powerful resource (www.extrameta.org) that expands the transcriptional landscape of exercise adaptation by extending previously known responses and their regulatory networks, and identifying novel modality-, time-, age-, and sex-associated changes.

494-P: Canagliflozin Prevents Hyperglycemia-Associated Muscle Extracellular Matrix Accumulation and Restores the Adaptive Response to Aerobic Exercise

In rodent models and humans, hyperglycemia is associated with an impaired adaptive response to aerobic exercise, which includes blunted improvements in aerobic capacity and impaired aerobic remodeling of skeletal muscle. To test whether glucose lowering therapy can restore the response to exercise, aerobic training studies were performed on hyperglycemic mice treated with or without the SGLT2 inhibitor, Canagliflozin (CANA) for 16-wks. Hyperglycemia was induced using two injections of streptozotocin (STZ; 40 mg/kg). A cohort of STZ-treated mice were administered CANA in their food (30 mg/kg/day), which normalized blood glucose to the level of untreated normoglycemic controls. The adaptive response to aerobic exercise training was blunted in STZ compared to control, but was restored by CANA treatment. Following training, CANA had improved aerobic exercise capacity (VO2peak), higher capillary density in cardiac and skeletal muscle, and a more oxidative fiber-type in skeletal muscle, compared to STZ. Recent work implicates glucose-induced accumulation of the skeletal muscle extracellular matrix (ECM), leading to hyper-activation of JNK/SMAD2 mechanical signaling after acute exercise as potential mechanisms underlying low exercise response. Consistent with this, STZ had significant accumulation of muscle ECM compared to control which was prevented by treatment with CANA, as assessed by histological staining. In addition, hyper-activation of JNK/SMAD2 mechanical signaling after a bout of acute exercise was 2-fold higher in STZ compared to control, but was normalized by CANA. These data demonstrate that hyperglycemia-associated impairments in exercise adaptation can be ameliorated by Canagliflozin treatment. Moreover, we identify skeletal muscle ECM accumulation and JNK/SMAD2 hyper-activation as potential mechanisms for impaired aerobic adaptation with hyperglycemia. Disclosure T. Macdonald: None. P. Pattamaprapanont: None. S. J. Lessard: None. Funding National Institutes of Health (R01DK124258)

Serotonin 1A agonist and cardiopulmonary improvements with whole-body exercise in acute, high-level spinal cord injury: A retrospective analysis

High-level spinal cord injury (SCI) can result in spinal and supraspinal respiratory control deficits leading to insufficient ventilatory responses to exercise and training-related adaptations. We hypothesized a serotonin agonist, known to improve respiratory function in animal models, would improve adaptations to whole-body functional electrical stimulation (FES) exercise training in patients with acute high-level SCI. We identified ten patients (< 2 years of injury with SCI from C4-T3) in our program who had performed six months of FES-row training while on the Buspirone, a serotonin 1A agonist (29 ± 17 mg/day), between 2012 and 2018. We also identified well-matched individuals who trained for six months but not on Buspirone ( n = 11). A peak incremental FES-rowing exercise test and resting pulmonary function test had been performed before and after training. Those on Buspirone demonstrated greater increases in peak oxygen consumption (VO 2 peak: +0.24 ± 0.23 vs. +0.10 ± 0.13 L/min, P = 0.08) and peak ventilation (VEpeak: +6.5 ± 8.1 vs. -0.7 ± 6.9 L/min, P < 0.05) compared to control. In addition, changes in VO 2 peak and VEpeak were correlated across all patients ( r = 0.63, P< 0.01), but most strongly in those on Buspirone ( r = 0.85, P < 0.01). Furthermore, changes in respiratory function correlated to increased peak tidal volume in the Buspirone group ( r > 0.66, P < 0.05). These results suggest Buspirone improves cardiorespiratory adaptations to FES-exercise training in individuals with acute, high-level SCI. The strong association between increases in ventilatory and aerobic capacities suggests improved respiratory function is a mechanism, however controlled studies are needed to determine if this preliminary finding is reproducible.

Higher Protein Intake Does Not Potentiate Skeletal Muscle Vitamin D Receptor

Abstract Objectives The loss of muscle mass with age increases not only risk of functional impairment, but also development and exacerbation of cardiometabolic disease. While dietary protein intake and habitual resistance exercise are traditional strategies to offset age-related decrements in lean mass, it is important to define the role of other regulatory nutrients in this process. Dietary vitamin D (VD) has received particular interest as muscle vitamin D receptor (VDR) is associated with hypertrophy. Importantly, beyond being a significant source of high-quality protein, animal-based protein foods are also rich in VD. While previous efforts have investigated the provision of protein and/or VD supplements during a resistance training program, the influence of dietary protein composition and diet-derived VD on resistance exercise adaptations remains unknown. Methods Forty-one middle-aged adults (mean ± SD: age 50 ± 8 y, BMI 27 ± 4 kg/m2, M = 19, F = 22) were stratified and randomized to consume either high (1.68 ± 0.26 g/kg/d) or moderate (1.16 ± 0.19 g/kg/d) amounts of animal-based protein during a 10-week dietary counseling-controlled resistance training program. Dietary intake was monitored by biweekly 3d diet records (ASA24). Dual-energy x-ray absorptiometry and muscle biopsies were performed pre- and post-intervention. Total RNA was extracted and reverse-transcribed for muscle gene expression by quantitative polymerase chain reaction. Intervention outcomes and their relationships were analyzed using linear mixed effects models and repeated measures correlation, respectively, by R. Results VDR gene expression increased regardless of condition (P = 0.007; 95% CI: 0.13, 0.84). Upregulation of VDR expression was correlated with gains in appendicular lean mass (r = 0.44; P = 0.011; CI: 0.10, 0.68). While protein intake did not affect VDR expression, animal-based protein diet density (servings/1000 kcal) was modestly correlated with VDR expression (r = 0.42; P = 0.014; CI: 0.08, 0.67). There was no relationship between dietary VD and VDR expression. Conclusions Our results suggests that moderate dietary protein intake is sufficient to support resistance exercise-induced VDR upregulation and lean mass gain in middle-aged adults. Funding Sources Funded in part by the Beef Checkoff. CFM funded by JBT Fellowship, UIUC.

Marching to the Beet: The effect of dietary nitrate supplementation on high altitude exercise performance and adaptation during a military trekking expedition

PurposeThe aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia). MethodsThis was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28 ± 12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70 ml dose per day of either BRJ (~12.5 mmol nitrate per day; n = 11) or non-nitrate calorie matched control (n = 11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800 m) reached on day 17 of the expedition. Data were collected at baseline (44 m altitude), at 2350 m (day 9), 3400 m (day 12) and 4800 m (day 17). ResultsBRJ enhanced the salivary levels of nitrite (p = 0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=<0.001). Harvard Step Test fitness scores significantly declined at 4800 m in the control group (p = 0.003) compared with baseline. In contrast, there was no decline in fitness scores at 4800 m compared with baseline (p = 0.26) in the BRJ group. Heart rate recovery speed following exercise at 4800 m was significantly prolonged in the control group (p=<0.01) but was unchanged in the BRJ group (p = 0.61). BRJ did not affect the burden of HA illness (p = 1.00). ConclusionsBRJ increases salivary nitrite levels and ameliorates the decline in fitness at altitude but does not affect the occurrence of HA illness.

Changes in Plasma Bioactive Lipids and Inflammatory Markers during a Half-Marathon in Trained Athletes

Background: Exercise may affect lipid profile which in turn is related to inflammation, although changes of ceramides, diacylglycerols-DAG and sphingomyelin-SM and their relationship with inflammatory parameters following a half-marathon have never been examined. Methods: Ceramides, DAG and SM, and markers of inflammation (soluble fractalkine-CX3CL1, vascular endothelial growth factor-VEGF, interleukin6-IL-6 and tumor necrosis factorα-TNFα) were evaluated in trained half-marathoners before, post-race (withdrawal within 20 min after the race end) and 24 h after. Results: IL-6 and CX3CL1 increased immediately after the race, returning to baseline after 24 h. Total ceramides and total DAG significantly decreased post-race. Several ceramide classes decreased after exercise, while only one of the DAG (36:3) changed significantly. Total SM and specific species did not significantly change. Conclusion: Some inflammatory parameters (IL-6 and CX3CL1) transiently increased after the race, and, being reversible, these changes might represent a physiological response to acute exercise rather than a damage-related response. The decrease of specific lipid classes, i.e., DAGs and ceramides, and the lack of their relationship with inflammatory parameters, suggest their involvement in beneficial training effects, opening promising research perspectives to identify additional mechanisms of aerobic exercise adaptation.

Exercise Is Medicine…and the Dose Matters.

The cellular events underpinning exercise adaptation have long been studied since Holloszy's novel findings in rodents over 50 years ago (Holloszy, 1967). Contemporary advances in laboratory techniques have allowed researchers to further explore physiological adaptations to physical activity, and much attention has been given to elucidating the distinct biochemical responses to exercise of varying intensities. More specifically, comparison of high intensity interval training (HIIT) or sprint interval training (SIT), to moderate intensity continuous training (MICT) has been an area of great interest among exercise physiologists. Spearheading these investigations, Burgomaster and colleagues provided evidence for robust and comparable metabolic adaptations when 6-weeks of low-volume SIT was pitted against conventional MICT, despite markedly reduced total training volume in the SIT group (66% less time, 90% less energy expenditure) (Burgomaster et al., 2008). Follow-up studies supporting these findings have provided continued enthusiasm for HIIT/SIT as a time-efficient strategy to improve cardiometabolic health (Gillen and Gibala, 2014; Gillen et al., 2016; Wolfe et al., 2020). HIIT has since become one of the most popular fitness trends as reported by the American College of Sports Medicine (ACSM) (#5 in 2021 survey) (Thompson, 2021). While we acknowledge these findings and are advocates for HIIT, we feel as though it is also important to appreciate the discrepant nature of HIIT and MICT, which may foster unique physiological adaptations with relevant health implications. Few, if any of these adaptations are mutually exclusive, but their magnitude may vary in a manner that should be considered to when determining exercise prescription.

Endurance Exercise Preconditioning Modulates Soleus Muscle Drug Transporter Expression and Doxorubicin Accumulation

Doxorubicin (DOX) is an anthracycline antibiotic used to treat a wide variety of cancers. While DOX is highly effective in reducing tumor burden, its clinical use is limited due to off-target effects to skeletal muscle. The toxic effects of DOX promotes skeletal muscle atrophy and weakness, resulting in patient fatigue, exercise intolerance, and reduced quality of life. Therefore, it is necessary to develop therapeutic countermeasures to prevent these debilitating side-effects. In this regard, it is established that endurance exercise preconditioning results in a phenotype that is resistant to DOX-induced skeletal muscle dysfunction. While the mechanisms for exercise-induced protection remain unclear, reports suggests that an exercise-induced reduction in skeletal muscle DOX accumulation plays an important role. However, the exercise adaptations which promote the reduction in DOX skeletal muscle localization are unknown. Therefore, the goal of this study was to determine if exercise preconditioning elicits changes in the expression of drug transporters in the soleus muscle. To test this, female Sprague-Dawley rats completed 10 days of treadmill exercise training (1hr/day; ~70% VO2Max; 30 m/min; 0% grade). Twenty-four hours after the last exercise bout, animals were treated with an acute bolus dose of DOX (20 mg/kg i.p.). Our results confirm that endurance exercise preconditioning is sufficient to reduce soleus DOX accumulation. In addition, exercise preconditioning significantly increased the expression of the DOX export proteins ABCC6 and ABCC10 (p<0.05). Exercise training was also a sufficient stimulus to decrease expression of the solute carrier transporter family members SLC22A4, SLC22A5, SLC28A1, SLC28A3, and SLCO2B1 (p<0.05), which have been shown to influence DOX cellular influx. Therefore, endurance exercise may reduce soleus DOX accumulation and protect against skeletal muscle dysfunction through beneficial modulation of genes capable of DOX transport.