Stem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice.

Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22-24 months) compared to saline-injected aged-matched controls. Secretome delivery substantially increased whole-body lean mass and decreased fat mass, corresponding to higher myofiber cross-sectional area and smaller adipocyte size, respectively. Secretome-treated mice also had greater whole-body physical function (grip strength and rotarod performance) and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome-treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, collagen IV turnover, reduced intramuscular lipids, and greater Akt and hormone sensitive lipase phosphorylation in adipose tissue. Finally, secretome treatment in vitro directly enhanced muscle cell growth and IL-6 production, and in adipocytes, it reduced lipid content and improved insulin sensitivity. Moreover, indirect treatment with secretome-treated myotube culture media also enhanced muscle cell growth and adipocyte size reduction. Together, these data suggest that intramuscular treatment with a stem cell secretome improves whole-body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice.

Divergent mechanisms regulate TLR4 expression on peripheral blood mononuclear cells following workload-matched exercise in normoxic and hypoxic environments.

Exercise in hypoxia increases immune responses compared with normoxic exercise, and while Toll-like receptor 4 (TLR4) is implicated in these responses, its regulation remains undefined. The purpose of this study was to 1) investigate TLR4 regulation during workload-matched endurance exercise in normoxic and hypoxic conditions in vivo and 2) determine the independent effects of hypoxia and muscle contractions on TLR4 expression in vitro. Eight recreationally active men cycled for 1 h at 65% of their V̇o2max in normoxia (630 mmHg) and in hypobaric hypoxia (440 mmHg). Exercise in normoxia decreased TLR4 expressed on peripheral blood mononuclear cells (PBMCs), had no effect on the expression of inhibitor of κBα (IκBα), and increased the concentration of soluble TLR4 (sTLR4) in circulation. In contrast, exercise in hypoxia decreased the expression of TLR4 and IκBα in PBMCs, and sTLR4 in circulation. Markers of physiological stress were higher during exercise in hypoxia, correlating with markers of intestinal barrier damage, circulating lipopolysaccharides (LPS), and a concurrent decrease in circulating sTLR4, suggesting heightened TLR4 activation, internalization, and degradation in response to escalating physiological strain. In vitro, both hypoxia and myotube contractions independently, and in combination, reduced TLR4 expressed on C2C12 myotubes, and these effects were dependent on hypoxia-inducible factor 1 (HIF-1). In summary, the regulation of TLR4 varies depending on the physiological stress during exercise. To our knowledge, our study provides the first evidence of exercise-induced effects on sTLR4 in vivo and highlights the essential role of HIF-1 in the reduction of TLR4 during contraction and hypoxia in vitro.NEW & NOTEWORTHY We provide the first evidence of exercise affecting soluble Toll-like receptor 4 (sTLR4), a TLR4 ligand decoy receptor. We found that the degree of exercise-induced physiological stress influences TLR4 regulation on peripheral blood mononuclear cells (PBMCs). Moderate-intensity exercise reduces PBMC TLR4 and increases circulating sTLR4. Conversely, workload-matched exercise in hypoxia induces greater physiological stress, intestinal barrier damage, circulating lipopolysaccharides, and reduces both TLR4 and sTLR4, suggesting heightened TLR4 activation, internalization, and degradation under increased strain.

Treadmill training does not enhance skeletal muscle recovery following disuse atrophy in older male mice.

Introduction: A hallmark of aging is poor muscle recovery following disuse atrophy. Efficacious strategies to enhance muscle recovery following disuse atrophy in aging are non-existent. Prior exercise training could result in favorable muscle morphological and cellular adaptations that may promote muscle recovery in aging. Here, we characterized the impact of exercise training on skeletal muscle inflammatory and metabolic profiles and cellular remodeling and function, together with femoral artery reactivity prior to and following recovery from disuse atrophy in aged male mice. We hypothesized that 12 weeks of treadmill training in aged male mice would improve skeletal muscle cellular remodeling at baseline and during recovery from disuse atrophy, resulting in improved muscle regrowth. Methods: Physical performance, ex vivo muscle and vascular function, tissue and organ mass, hindlimb muscle cellular remodeling (macrophage, satellite cell, capillary, myofiber size, and fibrosis), and proteolytic, inflammatory, and metabolic muscle transcripts were evaluated in aged exercise-trained and sedentary mice. Results: We found that at baseline following exercise training (vs. sedentary mice), exercise capacity and physical function increased, fat mass decreased, and endothelial function improved. However, exercise training did not alter tibialis anterior or gastrocnemius muscle transcriptional profile, macrophage, satellite cell, capillarity or collagen content, or myofiber size and only tended to increase tibialis mass during recovery from disuse atrophy. Conclusion: While exercise training in old male mice improved endothelial function, physical performance, and whole-body tissue composition as anticipated, 12 weeks of treadmill training had limited impact on skeletal muscle remodeling at baseline or in response to recovery following disuse atrophy.

Effect of heat stress on heat shock protein expression and hypertrophy-related signaling in the skeletal muscle of trained individuals.

Muscle mass is balanced between hypertrophy and atrophy by cellular processes, including activation of the protein kinase B-mechanistic target of rapamycin (Akt-mTOR) signaling cascade. Stressors apart from exercise and nutrition, such as heat stress, can stimulate the heat shock protein A (HSPA) and C (HSPC) families alongside hypertrophic signaling factors and muscle growth. The effects of heat stress on HSP expression and Akt-mTOR activation in human skeletal muscle and their magnitude of activation compared with known hypertrophic stimuli are unclear. Here, we show a single session of whole body heat stress following resistance exercise increases the expression of HSPA and activation of the Akt-mTOR cascade in skeletal muscle compared with resistance exercise in a healthy, resistance-trained population. Heat stress alone may also exert similar effects, though the responses are notably variable and require further investigation. In addition, acute heat stress in C2C12 muscle cells enhanced myotube growth and myogenic fusion, albeit to a lesser degree than growth factor-mediated hypertrophy. Though the mechanisms by which heat stress stimulates hypertrophy-related signaling and the potential mechanistic role of HSPs remain unclear, these findings provide additional evidence implicating heat stress as a novel growth stimulus when combined with resistance exercise in human skeletal muscle and alone in isolated murine muscle cells. We believe these findings will help drive further applied and mechanistic investigation into how heat stress influences muscular hypertrophy and atrophy.NEW & NOTEWORTHY We show that acute resistance exercise followed by whole body heat stress increases the expression of HSPA and increases activation of the Akt-mTOR cascade in a physically active and resistance-trained population.

Stimulated myotube contractions regulate membrane-bound and soluble TLR4 to prevent LPS-induced signaling and myotube atrophy in skeletal muscle cells.

Toll-like receptor 4 (TLR4) activation by lipopolysaccharides (LPS) increases proinflammatory cytokine production and upregulation of muscle atrophy signaling pathways. Muscle contractions can suppress LPS/TLR4 axis activation by reducing the protein expression of TLR4 on immune cells. However, the mechanism by which muscle contractions decrease TLR4 remains undefined. Moreover, it is not clear whether muscle contractions affect TLR4 expressed on skeletal muscle cells. The purpose of this study was to uncover the nature and mechanisms by which stimulated myotube contractions using electrical pulse stimulation (EPS) as an in vitro model of skeletal muscle contractions affect TLR4 expression and intracellular signaling to combat LPS-induced muscle atrophy. C2C12 myotubes were stimulated to contract via EPS with and without subsequent LPS exposure. We then examined the isolated effects of conditioned media (CM) collected following EPS and soluble TLR4 (sTLR4) alone on LPS-induced myotube atrophy. Exposure to LPS decreased membrane-bound and sTLR4, increased TLR4 signaling (decreased inhibitor of κBα), and induced myotube atrophy. However, EPS decreased membrane-bound TLR4, increased sTLR4, and prevented LPS-induced signaling and myotube atrophy. CM, which contained elevated levels of sTLR4, prevented LPS-induced upregulation of atrophy-related gene transcripts muscle ring finger 1 (MuRF1) and atrogin-1 and reduced myotube atrophy. Recombinant sTLR4 added to media prevented LPS-induced myotube atrophy. In summary, our study provides the first evidence that sTLR4 has anticatabolic effects by reducing TLR4-mediated signaling and atrophy. In addition, the study reveals a novel finding, by demonstrating that stimulated myotube contractions decrease membrane-bound TLR4 and increase the secretion of sTLR4 by myotubes.NEW & NOTEWORTHY Excessive Toll-like receptor 4 (TLR4) activation causes muscle atrophy. Muscle contractions can limit TLR4 activation on immune cells, but its impact on TLR4 expressed on skeletal muscle cells remains unclear. Here, we demonstrate in C2C12 myotubes for the first time that stimulated myotube contractions reduce membrane-bound TLR4 and increase soluble TLR4, preventing TLR4-mediated signaling and myotube atrophy. Further analyses revealed soluble TLR4 independently prevents myotube atrophy, supporting a potential therapeutic role in combating TLR4-mediated atrophy.

Circulating markers of intestinal barrier injury and inflammation following exertion in hypobaric hypoxia.

Hypoxia induced intestinal barrier injury, microbial translocation, and local/systemic inflammation may contribute to high-altitude associated gastrointestinal complications or symptoms of acute mountain sickness (AMS). Therefore, we tested the hypothesis that six-hours of hypobaric hypoxia increases circulating markers of intestinal barrier injury and inflammation. A secondary aim was to determine if the changes in these markers were different between those with and without AMS. Thirteen participants were exposed to six hours of hypobaric hypoxia, simulating an altitude of 4572 m. Participants completed two 30-minute bouts of exercise during the early hours of hypoxic exposure to mimic typical activity required by those at high altitude. Pre- and post-exposure blood samples were assessed for circulating markers of intestinal barrier injury and inflammation. Data below are presented as mean ± standard deviation or median [interquartile range]. Intestinal fatty acid binding protein (Δ251 [103-410] pg•mL-1; p = 0.002, d = 0.32), lipopolysaccharide binding protein (Δ2 ± 2.4 µg•mL-1; p = 0.011; d = 0.48), tumor necrosis factor-α (Δ10.2 [3-42.2] pg•mL-1; p = 0.005; d = 0.25), interleukin-1ß (Δ1.5 [0-6.7] pg•mL-1 p = 0.042; d = 0.18), and interleukin-1 receptor agonist (Δ3.4 [0.4-5.2] pg•mL-1p = 0.002; d = 0.23) increased from pre- to post-hypoxia. Six of the 13 participants developed AMS; however, the pre- to post-hypoxia changes for each marker were not different between those with and without AMS (p > 0.05 for all indices). These data provide evidence that high altitude exposures can lead to intestinal barrier injury, which may be an important consideration for mountaineers, military personnel, wildland firefighters, and athletes who travel to high altitudes to perform physical work or exercise.

Could Orthostatic Stress Responses Predict Acute Mountain Sickness Susceptibility Prior to High Altitude Travel? A Pilot Study.

Bellovary, Bryanne N., Andrew D. Wells, Zachary J. Fennel, Jeremy B. Ducharme, Jonathan M. Houck, Trevor J. Mayschak, Ann L. Gibson, Scott N. Drum, and Christine M. Mermier. Could orthostatic stress responses predict acute mountain sickness susceptibility before high altitude travel? A pilot study. High Alt Med Biol. 24:19-26, 2023. Purpose: This study assessed head-up tilt (HUT) responses in relation to acute mountain sickness (AMS)-susceptibility during hypoxic exposure. Materials and Methods: Fifteen participants completed three lab visits: (1) protocol familiarization and cycle maximal oxygen consumption (VO2max) test; (2) HUT test consisting of supine rest for 20 minutes followed by 70° tilting for ≤40 minutes; and (3) 6 hours of hypobaric hypoxic exposure (4,572 m) where participants performed two 30-minute cycling bouts separated by 1 hour at a 50% VO2max workload within the first 3 hours and rested when not exercising. During HUT, systolic blood pressure (SBP), diastolic blood pressure, heart rate (HR), and variability (blood pressure variability [BPV] and HR variability [HRV]) were measured continuously. The AMS scores were determined after 6 hours of exposure. Correlations determined relationships between HUT cardiovascular responses and AMS scores. Repeated-measures analysis of variance (ANOVA) assessed differences between those with and without AMS symptoms during HUT. Results: Higher AMS scores correlated with greater change in SBP variability (r = 0.52, p = 0.048) and blunted changes in HRV (root mean square of successive differences between normal heartbeats r = 0.81, p = 0.001, percentage of adjacent normal sinus intervals that differ by more than 50 milliseconds [pNN50] r = 0.87, p < 0.001) during HUT. A pNN50 interaction (p = 0.02) suggested elevated cardiac sympathetic activity at baseline and a blunted increase in cardiac sympathetic influence throughout HUT in those with AMS (pNN50 baseline: AMS = 26.2% ± 15.3%, no AMS = 51.0% ± 13.5%; first 3 minutes into HUT: AMS = 17.2% ± 19.1%, no AMS = 17.1% ± 10.9%; end of HUT: AMS = 6.2% ± 9.1%, no AMS 11.0% ± 10.0%). Conclusions: The results suggest autonomic responses via HUT differ in AMS-susceptible individuals. Changes in HRV and BPV during HUT may be a promising predictive measurement for AMS-susceptibility, but further research is needed for confirmation.

Autophagy in peripheral blood mononuclear cells is associated with body fat percentage.

CONTEXT: Numerous chronic conditions including obesity exhibit autophagic dysfunction. Association of immune cell autophagic marker regulation by body fat percentage (%BF) is unknown. OBJECTIVE: Investigate autophagy activity in peripheral blood mononuclear cells (PBMCs) of adults with distinct %BFs and obesity-related circulating inflammatory markers. MATERIALS AND METHODS: Sixteen individuals (eight males) with %BF above (n = 8, 36.9 ± 3.6 years, 27.1 ± 8.1%BF) and below (n = 8, 37.1 ± 3.7 years, 13.3 ± 3.7%BF) their age- and sex-specific 50th percentile value based on the American College Sports Medicine guidelines participated. Body fat percentage was calculated from hydrostatic weighing. PBMCs were isolated from venous blood, and PBMC autophagic flux markers (LC3-I, LC3-II, and p62) were measured via Western blot. CRP, resistin, leptin, and adiponectin were measured via ELISA. RESULTS: LC3-II/LC3-I ratio correlated with %BF (r=-0.56, p=.023). Insulin (p=.05) and CRP (p=.018) were higher in high %BF participants. DISCUSSION AND CONCLUSIONS: Autophagic activity markers in PBMCs correlate with %BF, but are not different between %BF groups.

Ibuprofen Increases Markers of Intestinal Barrier Injury But Suppresses Inflammation at Rest and After Exercise in Hypoxia.

PURPOSE: The purpose of this study was to evaluate the effects of acute ibuprofen consumption (2 × 600-mg doses) on markers of enterocyte injury, intestinal barrier dysfunction, inflammation, and symptoms of gastrointestinal (GI) distress at rest and after exercise in hypobaric hypoxia. METHODS: Using a randomized double-blind placebo-controlled crossover design, nine men (age, 28 ± 3 yr; weight, 75.4 ± 10.5 kg; height, 175 ± 7 cm; body fat, 12.9% ± 5%; V̇O 2 peak at 440 torr, 3.11 ± 0.65 L·min -1 ) completed a total of three visits including baseline testing and two experimental trials (placebo and ibuprofen) in a hypobaric chamber simulating an altitude of 4300 m. Preexercise and postexercise blood samples were assayed for intestinal fatty acid binding protein (I-FABP), ileal bile acid binding protein, soluble cluster of differentiation 14, lipopolysaccharide binding protein, monocyte chemoattractant protein-1, tumor necrosis factor α (TNF-α), interleukin-1ß, and interleukin-10. Intestinal permeability was assessed using a dual sugar absorption test (urine lactulose-to-rhamnose ratio). RESULTS: Resting I-FABP (906 ± 395 vs 1168 ± 581 pg·mL -1 ; P = 0.008) and soluble cluster of differentiation 14 (1512 ± 297 vs 1642 ± 313 ng·mL -1 ; P = 0.014) were elevated in the ibuprofen trial. Likewise, the urine lactulose-to-rhamnose ratio (0.217 vs 0.295; P = 0.047) and the preexercise to postexercise change in I-FABP (277 ± 308 vs 498 ± 479 pg·mL -1 ; P = 0.021) were greater in the ibuprofen trial. Participants also reported greater upper GI symptoms in the ibuprofen trial ( P = 0.031). However, monocyte chemoattractant protein-1 ( P = 0.007) and TNF-α ( P = 0.047) were lower throughout the ibuprofen trial compared with placebo (main effect of condition). CONCLUSIONS: These data demonstrate that acute ibuprofen ingestion aggravates markers of enterocyte injury and intestinal barrier dysfunction at rest and after exercise in hypoxia. However, ibuprofen seems to suppress circulating markers of inflammation.

Body fat percentage is independently and inversely associated with serum antibody responses to SARS-CoV-2 mRNA vaccines.

Vaccination is widely considered the most effective preventative strategy to protect against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. An individual's exercise habits, and physical fitness have been shown to impact the immune response following vaccination using traditional vaccine platforms, but their effects are not well characterized following administration of newer vaccination technology (mRNA vaccines). We investigated these effects on the magnitude of antibody responses following SARS-CoV-2 mRNA vaccination while accounting for known covariates (age, sex, time since vaccination, and the type of vaccine administered). Adults of varying fitness levels (18-65 years; N = 50) who had received either the Moderna or Pfizer SARS-CoV-2 mRNA vaccine between 2 weeks and 6 months prior, completed health history and physical activity questionnaires, had their blood drawn, body composition, cardiorespiratory fitness, and strength assessed. Multiple linear regressions assessed the effect of percent body fat, hand grip strength, cardiorespiratory fitness, and physical activity levels on the magnitude of receptor binding domain protein (RBD) and spike protein subunit 1 (S1) and 2 (S2) while accounting for known covariates. Body fat percentage was inversely associated with the magnitude of S1 (p = 0.006, ß = - 366.56), RBD (p = 0.003, ß = - 249.30), and S2 (p = 0.106, ß = - 190.08) antibodies present in the serum following SARS-CoV-2 mRNA vaccination. Given the increasing number of infections, variants, and the known waning effects of vaccination, future mRNA vaccinations such as boosters are encouraged to sustain immunity; reducing excess body fat may improve the efficacy of these vaccinations.

The heat shock connection: skeletal muscle hypertrophy and atrophy.

Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving health and performance across the lifespan. Based largely on cellular and animal models, there is some evidence that various forms of heat stress with or without resistance exercise may enhance skeletal muscle growth or reduce its loss. It is not clear whether these stimuli are similarly effective in humans or meaningful compared with exercise alone across various heating methodologies. Furthermore, the magnitude by which heat stress may influence whole body thermoregulatory responses and the connection to skeletal muscle adaptation remains ambiguous. Finally, the underlying mechanisms, which may include interaction between relevant heat shock proteins and intracellular hypertrophy and atrophy related factors, remain unclear. In this narrative review, we examine the relevant literature regarding heat stress alone or in combination with resistance exercise emphasizing skeletal muscle hypertrophy and atrophy across cellular and animal models, as well as human investigations. In addition, we present working mechanistic theories for heat shock protein-mediated signaling effects regarding hypertrophy and atrophy-related signaling processes. Importantly, continued research is necessary to determine the practical effects and mechanisms of heat stress with and without resistance exercise on skeletal muscle function via growth and maintenance.

Exercise in hypobaric hypoxia increases markers of intestinal injury and symptoms of gastrointestinal distress.

NEW FINDINGS: What is the central question of this study? What is the effect of hypobaric hypoxia on markers of exercise-induced intestinal injury and symptoms of gastrointestinal (GI) distress? What is the main finding and its importance? Exercise performed at 4300 m of simulated altitude increased intestinal fatty acid binding protein (I-FABP), claudin-3 (CLDN-3) and lipopolysaccharide binding protein (LBP), which together suggest that exercise-induced intestinal injury may be aggravated by concurrent hypoxic exposure. Increases in I-FABP, LBP and CLDN-3 were correlated to exercise-induced GI symptoms, providing some evidence of a link between intestinal barrier injury and symptoms of GI distress. ABSTRACT: We sought to determine the effect of exercise in hypobaric hypoxia on markers of intestinal injury and gastrointestinal (GI) symptoms. Using a randomized and counterbalanced design, nine males completed two experimental trials: one at local altitude of 1585 m (NORM) and one at 4300 m of simulated hypobaric hypoxia (HYP). Participants performed 60 min of cycling at a workload that elicited 65% of their NORM V̇O2max${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ . GI symptoms were assessed before and every 15 min during exercise. Pre- and post-exercise blood samples were assessed for intestinal fatty acid binding protein (I-FABP), claudin-3 (CLDN-3) and lipopolysaccharide binding protein (LBP). All participants reported at least one GI symptom in HYP compared to just one participant in NORM. I-FABP significantly increased from pre- to post-exercise in HYP (708 ± 191 to 1215 ± 518 pg ml-1 ; P = 0.011, d = 1.10) but not NORM (759 ± 224 to 828 ± 288 pg ml-1 ; P > 0.99, d = 0.27). CLDN-3 significantly increased from pre- to post-exercise in HYP (13.8 ± 0.9 to 15.3 ± 1.2 ng ml-1 ; P = 0.003, d = 1.19) but not NORM (13.7 ± 1.8 to 14.2 ± 1.6 ng ml-1 ; P = 0.435, d = 0.45). LBP significantly increased from pre- to post-exercise in HYP (10.8 ± 1.2 to 13.9 ± 2.8 µg ml-1 ; P = 0.006, d = 1.12) but not NORM (11.3 ± 1.1 to 11.7 ± 0.9 µg ml-1 ; P > 0.99, d = 0.32). I-FABP (d = 0.85), CLDN-3 (d = 0.95) and LBP (d = 0.69) were all significantly higher post-exercise in HYP compared to NORM (P ≤ 0.05). Overall GI discomfort was significantly correlated to ΔI-FABP (r = 0.71), ΔCLDN-3 (r = 0.70) and ΔLBP (r = 0.86). These data indicate that cycling exercise performed in hypobaric hypoxia can cause intestinal injury, which might cause some commonly reported GI symptoms.

A Metabolic Profile of Peripheral Heart Action Training.

Purpose: Peripheral heart action (PHA) is a style of circuit training that alternates upper and lower body resistance exercises with minimal rest between sets. The purpose of this study was to compare the metabolic demands of PHA to traditional hypertrophy training (TRAD) and to provide between sex comparison for both types of resistance training (RT). Methods: Twenty resistance-trained individuals underwent two bouts of volume-load matched RT: PHA and TRAD. We measured oxygen uptake (VO2), heart rate (HR), blood lactate (BL) concentration, rating of perceived exertion (RPE), excess post-exercise oxygen consumption (EPOC), and duration of each session. Results: PHA elicited significantly greater %VO2max (p < .001), %HRmax (p < .001), RPE (p < .001), and EPOC (p < .001) compared to TRAD. PHA was also completed in less time (p < .001). Compared to TRAD, BL was significantly higher at mid-exercise (p < .001), post-exercise (p < .001), and 5-min post-exercise (p < .001) during PHA. There were no between-sex differences for BL at any time-point for TRAD. However, during PHA, BL was significantly higher for males at mid-exercise (p = .04), post-exercise (p = .02), and 5-min post-exercise (p = .002). No between-sex differences were detected for HR, VO2, RPE, or duration for either style of RT. Conclusions: PHA is a time-effective and metabolically demanding circuit that may lead to strength and cardiorespiratory adaptations. Males produced more BL than females during PHA, but not TRAD, suggesting that they incurred more metabolic stress during the bout of circuit training.

Worth the Wait? Time Course of Supine Shifts in Body Water Compartments on Variables of Bioelectrical Impedance Analysis.

Bioelectrical impedance analysis (BIA) reference values are based on supine assessments. Little is known regarding the effects of time course shifts in body water compartments after assuming a supine position. The aim of this study was to characterize these effects and provide recommendations regarding the optimal waiting time to perform BIA. Thirty-eight healthy adults underwent BIA via the RJL Quantum Legacy analyzer immediately upon lying down and every 5 minutes for 15 minutes. Differences in resistance (R), reactance (Xc), intracellular (ICW), extracellular (ECW), total body water (TBW), body fat percentage (%BF), and phase angle (PhA) were assessed. There were small but significant increases in R, Xc, and %BF (all p<0.001), as well as small but significant decreases in ICW, ECW, and TBW (all p<0.001) over 15 minutes. No difference was observed for PhA (p=0.065). Average values changed over 15 minutes by +7.14Ω, +1.36Ω, -0.2L, -0.2L, -0.4L, +0.05° and +0.1% for R, Xc, ICW, ECW, TBW, PhA and %BF, respectively. BIA measurements are affected by shifts in body water compartments after assuming a supine position, but these differences lack clinical significance in healthy adults. Technicians working with healthy adults can perform BIA within 15 minutes after participants assume a supine position.

Comparison of resting metabolic rate prediction equations in college-aged adults.

Prediction equations have been considered an accurate method for estimating resting metabolic rate (RMR) across multiple populations, but their accuracy for college-aged individuals not on an athletics team remains to be determined. Sixty-two college-aged (18-30 yrs) males (n = 31) and females (n = 31) had their RMR measured (RMRm), using indirect calorimetry, and body composition assessed via air-displacement plethysmography. The World Health Organization (WHO), Mifflin-St Jeor (Mifflin), Harris-Benedict (HB), Cunningham, and Nelson equations were used to estimate RMR. No difference was observed between the Cunningham and RMRm regardless of sex (p ≥ 0.05). All other prediction equations estimated a significantly lower RMR for males (p < 0.05). The Mifflin and Nelson equations predicted an RMR that was significantly lower than RMRm for females (p < 0.05). When compared with RMRm, no difference was detected for females using the WHO, HB, or Cunningham (p ≥ 0.05). Only the Nelson equation predicted an RMR that was outside of the clinically acceptable range (±10% of RMRm) regardless of sex. The Cunningham, WHO, and HB equations can accurately predict RMR for college-aged males and females. RMR prediction equations used in this study are less accurate for those with greater RMRs. Novelty: For adults 18-30 years old that are not on an athletics team, the Cunningham equation can accurately predict RMR. The Nelson equation should not be used to predict RMR for this population. There is a systematic bias for RMR prediction equations to underestimate higher measured RMR values.

Heat acclimation during low-intensity exercise increases V̇O2max and Hsp72, but not markers of mitochondrial biogenesis and oxidative phosphorylation, in skeletal tissue.

NEW FINDINGS: What is the central question of this study? Heat acclimation increases tolerance to exercise performed in the heat and may improve maximal oxygen uptake (VO2 max) and performance in temperate environments. However, it is unknown if HA affects the expression of proteins related to mitochondrial biogenesis and oxidative capacity in skeletal muscle. What is the main finding and its importance? We showed that heat acclimation increased VO2 max in a temperate environment but did not change markers of mitochondrial biogenesis and oxidative phosphorylation in the skeletal muscle. ABSTRACT: Heat acclimation (HA) increases tolerance to exercise performed in the heat and may improve maximal oxygen uptake ( V̇O2max ) in temperate environments. However, it is unknown if HA affects the expression of proteins related to mitochondrial biogenesis and oxidative capacity in skeletal muscle. The purpose of this study was to investigate the effect of HA on skeletal muscle markers of mitochondrial biogenesis and oxidative phosphorylation in recreationally trained adults. Thirteen (7 males and 6 females) individuals underwent 10 days of HA. Participants performed two 45 min bouts of exercise (walking at 30-40% maximal velocity at 3% grade) with 10 min rest per session in a hot environment (∼42°C and 30-50% relative humidity). V̇O2max , ventilatory thresholds (VT), and protein expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), mitochondrial transcription factor A (TFAM), calcium/calmodulin-dependent protein kinase (CaMK), electron transport chain (ETC) complexes I-IV, and heat shock protein 72 (Hsp72) in skeletal muscle were measured pre- and post-HA. Comparing day 1 to day 10, HA was confirmed by lower resting core temperature (Tcore ) (P = 0.026), final Tcore (P < 0.0001), mean heart rate (HR) (P = 0.002), final HR (P = 0.003), mean ratings of perceived exertion (RPE) (P = 0.026) and final RPE (P = 0.028). Pre- to post-HA V̇O2max (P = 0.045) increased but VT1 (P = 0.263) and VT2 (P = 0.239) were unchanged. Hsp72 (P = 0.007) increased, but skeletal muscle protein expression (PGC-1α, P = 0.119; TFAM, P = 0.763; CaMK, P = 0.19; ETC I, P = 0.629; ETC II, P = 0.724; ETC III, P = 0.206; ETC IV, P = 0.496) were not affected with HA. HA during low-intensity exercise increased V̇O2max in a temperate environment and Hsp72 but it did not affect markers of mitochondrial biogenesis and oxidative phosphorylation in the skeletal muscle.