Respiratory Exchange Ratio Research Articles

Sex-specific role of high-fat diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus

BackgroundScientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice.MethodsTo investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis.ResultsWe observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress.ConclusionsOverall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.

MicroRNA-21 modulates brown adipose tissue adipogenesis and thermogenesis in a mouse model of polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with increased obesity, hyperandrogenism, and altered brown adipose tissue (BAT) thermogenesis. MicroRNAs play critical functions in brown adipocyte differentiation and maintenance. We aim to study the role of microRNA-21 (miR-21) in altered energy homeostasis and BAT thermogenesis in a PCOS mouse model of peripubertal androgen exposure.MethodsThree-week-old miR-21 knockout (miR21KO) or wild-type (WT) female mice were treated with dihydrotestosterone (DHT) or vehicle for 90 days. Body composition was determined by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured by indirect calorimetry. Androgen receptor (AR), and markers of adipogenesis, de novo lipogenesis, angiogenesis, extracellular matrix remodeling, and thermogenesis were quantified by RT-qPCR and/or Western-blot.ResultsMiR-21 ablation attenuated DHT-mediated increase in body weight while having no effect on fat or BAT mass. MiR-21 ablation attenuated DHT-mediated BAT AR upregulation. MiR-21 ablation did not alter EE; however, miR21KO DHT-treated mice have reduced VO2, VCO2, and RER. MiR-21 ablation reversed DHT-mediated decrease in food intake and increase in sleep time. MiR-21 ablation decreased some adipogenesis (Adipoq, Pparγ, and Cebpβ) and extracellular matrix remodeling (Mmp-9 and Timp-1) markers expression in DHT-treated mice. MiR-21 ablation abolished DHT-mediated increases in thermogenesis markers Cpt1a and Cpt1b, while decreasing CIDE-A expression.ConclusionsOur findings suggest that BAT miR-21 may play a role in regulating DHT-mediated thermogenic dysfunction in PCOS. Modulation of BAT miR-21 levels could be a novel therapeutic approach for the treatment of PCOS-associated metabolic derangements.

Assessment of cardiopulmonary capacity in deconditioned athletes because of knee injury.

An athlete's career inevitably goes through periods of forced physical exercise interruption like a knee injury. Advanced echocardiographic methods and cardiopulmonary exercise testing (CPET) are essential in evaluating athletes in the period elapsing after the injury. However, the feasibility of a maximal pre-surgery CPET and the capacity of resting advanced echocardiographic techniques to predict cardiorespiratory capacity still need to be clarified. We evaluated 28 non-professional athletes aged 18-52, involved in prevalently aerobic or alternate aerobic/anaerobic sports activities, affected by a knee pathology with indications for surgical treatment. The evaluation was performed at rest by trans-thoracic echocardiography, including global longitudinal strain (GLS) and myocardial work (MW) assessment, and during exercise by CPET. The percent-predicted peak oxygen consumption (peak VO<inf>2</inf>%) was 82.8±13.7%, the mean respiratory exchange ratio was 1.16±0.08, and the mean ventilation/carbon dioxide (V<inf>E</inf>/VCO<inf>2</inf>) slope was 24.23±3.36. Peak VO<inf>2</inf>% negatively correlated with GLS (r=-0.518, P=0.003) and global wasted work (GWW) (r =-0.441, P=0.015) and positively correlated with global work efficiency (GWE) (r=0.455, P=0.012). Finally, we found that the V<inf>E</inf>/VCO<inf>2</inf> slope during exercise was negatively correlated with GWE (r=-0.585, P=0.001) and positively correlated with GWW (r=0.499, P=0.005). A maximal CPET can be obtained in deconditioned athletes because of a knee injury, allowing a comprehensive functional pre-surgery evaluation. In these patients, peak VO<inf>2</inf> is reduced due to decreased physical activity after injury; however, a lower cardiopulmonary efficiency may be a concause of the injury itself. In addition, we demonstrated that the MW indexes obtained at rest could predict exercise capacity and ventilatory efficiency as evaluated by CPET.

Assessment of cardiorespiratory function in adolescent athletes affected by COVID-19: a comparative analysis

Background and Study Aim. Given the global spread of COVID-19 and its profound effects on public health, understanding its impact on the physical health and performance of young athletes is crucial for developing guidelines to support their recovery and well-being. The goal of this research was to assess the impact of the COVID-19 infection and possible consequences on the functional abilities of schoolchild athletes, and determine whether there are differences compared to their peers who did not suffer the infection. Material and Methods. This study involved 100 teenagers (median age 15.7±1.167), who engage in two different sports (basketball and soccer), divided into two groups. The first group comprised young athletes (n=53, age 15.79±1.854) who had contracted COVID-19 and underwent 14 days of home isolation. The second group consisted of healthy child athletes (n=47, age 15.60±1.313). Participants underwent a comprehensive pre-participation sports medical examination, which included a cardiopulmonary exercise test (CPET) on a treadmill. CPET assessed various physiological parameters: maximum oxygen consumption (VO2max); heart rates at the first and second ventilatory thresholds (HR at VT1 and HR at VT2); respiratory exchange ratio (RER); maximal pulmonary ventilation (VEmax); ventilatory efficiency (VE/VCO2); oxygen pulse (O2/HR); maximum heart rate (HRmax); three-minute heart rate recovery; and potential electrocardiographic changes. Results. The results indicate that COVID-19 infection has led to statistically significant impairments in the cardiorespiratory functions of child athletes. Notably, there were significant reductions in maximum oxygen consumption (VO2max), maximal pulmonary ventilation (VEmax), oxygen pulse (O2/HR), as well as heart rates at the first ventilatory threshold (HR at VT1), maximum heart rate (HRmax), and heart rate recovery following maximal effort, all demonstrating p-values less than 0.05. Conclusions. The assessed parameters demonstrated that the functions were statistically significantly impaired in child athletes who had recovered from COVID-19 compared to their healthy peers of the same age. However, the infection appeared to have a minimal impact on heart rate variability at ventilatory thresholds. These findings offer valuable insights for coaches and sports medicine physicians in adjusting training programs and supporting the rehabilitation process for young adolescent athletes resuming their training after recovering from COVID-19.

The Liver Circadian Metabolic Homeostasis Influence by Combining Ketogenic Diet with Exercise.

The ketogenic diet (KD) and regular exercise (EX) are both capable of orchestrating circadian metabolism homeostasis during losing weight. However, the combined effects of these two factors on circadian metabolism remain poorly understood. To determine if the combined treatment yields a superimposed physiological phenotype, we measured weight loss, white adipose, the respiratory exchange ratio (RER), heat production, and activity parameters in individual and combined treatment groups. Surprisingly, none of these metrics displayed a cumulative effect when administered in the combined treatment approach. Additionally, we investigated the impact of combination therapy on molecular homeostasis through using high-throughput liver transcriptomic approaches. The results revealed that individual and combined treatments can reprogram the circadian rhythm; yet, the combined group exhibited a minimum quantity of cyclic transcript genes. Noteworthy, the amplitude of 24 h circadian expression genes was not significantly increased in the combination treatment, indicating that the combined approach has non-overlapping effects on maintenance peripheral metabolism homeostasis. This may be due to the liver requiring less ketogenic and gluconeogenic potential during metabolic processes. This research suggests that combined treatment may have adverse effects on the body's homeostasis and provide crucial insights for the homeostatic health of athletes or individuals who wish to lose weight.

Altered glucose kinetics occurs with aging: a new outlook on metabolic flexibility.

Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios [RER = carbon dioxide production (V̇co2)/oxygen consumption (V̇o2)] during a 2-h 75-g oral glucose tolerance test (OGTT). After an 12-h overnight fast, 28 participants, 15 young (21-35 yr; 7 men and 8 women) and 13 older (60-80 yr; 7 men and 6 women), received venous primed-continuous infusions of [6,6-2H]glucose and [3-13C]lactate with a [Formula: see text] bolus. After a 90-min metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 min post glucose consumption, peaked at 60 min, and remained elevated. As assessed by rates of appearance (Ra) and disposal (Rd) and metabolic clearance rate (MCR), glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population after the oral glucose challenge. Finally, there were no differences in 12-h fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population after a glucose challenge. Furthermore, those physiological deficits are not detected from changes in RER during an OGTT.NEW & NOTEWORTHY To determine metabolic flexibility in response to an OGTT, we studied healthy young and older men and women to determine glucose kinetics and changes in RER. Compared to young subjects, glucose kinetics were suppressed in older healthy individuals during an OGTT. Surprisingly, the age-related changes in glucose flux were not reflected in RER measurements; thus, RER measurements do not give a complete view of metabolic flexibility in healthy individuals.

Sex Differences in Energy Metabolism: A Female-Oriented Discussion.

The purpose of this review is to delineate aspects of energy metabolism at rest and during exercise that may be subject to sex differences and the potential underlying mechanisms involved. It focuses on distinct aspects of female physiology with an oriented discussion following the reproductive life stages of healthy, eumenorrheic females, including premenopausal time frames, pregnancy, perimenopause, and menopause. Finally, this review aims to address methodological challenges surrounding sexual dimorphism in energy metabolism investigations and confounding factors in this field. During resting conditions, females tend to have higher rates of non-oxidative free fatty acid clearance, which could contribute to lower respiratory exchange ratio measures. At the same time, carbohydrate energy metabolism findings are mixed. In general, females favor lipid energy metabolism during moderate-intensity exercise, while men favor carbohydrate energy metabolism. Factors such as age, dietary intake, genetics, and methodological decisions confound study findings, including properly identifying and reporting the menstrual cycle phase when female subjects are eumenorrheic. Pregnancy presents a unique shift in physiological systems, including energy metabolism, which can be observed at rest and during exercise. Changes in body composition and hormonal levels during the post-menopausal period directly impact energy metabolism, specifically lipid metabolism. This change in physiological state factors into the evidence showing a reduction in our understanding of sex differences in lipid metabolism during exercise in older adults. This review reveals a need for a focused understanding of female energy metabolism that could help exercise and nutrition professionals optimize female health and performance across the lifespan.

Repeated Bout Effect of Downhill Running on Physiological Markers of Effort and Post Exercise Perception of Soreness in Trained Female Distance Runners.

This study examined the effect of repeated bouts of level and downhill running on physiological markers of effort and exercise-induced muscle soreness in trained female distance runners. Ten participants (Age: 24.4 ± 2.0 years; V̇O2peak: 52.9 ± 1.1 mL·kg-1·min-1), naïve to downhill running, completed six alternate 5 min trials of level and downhill running (-15%) at a 70% velocity at V̇O2peak on two occasions, three weeks apart. Perceived muscle soreness was measured upon completion and in the 72 h post exercise. V̇O2, Heart Rate (HR), Blood Lactate (BLa), and Respiratory Exchange Ratio (RER) were lower running downhill (p < 0.016, ηp2 > 0.541). For the first downhill run, Rating of Perceived Exertion (RPE) was higher compared to that for level running (p = 0.051; d = 0.447), but for the remaining trials, RPE was lower when running downhill (p < 0.004; d > 0.745). V̇O2, HR, and RER were not different in the second bout (p > 0.070, ηp2 < 0.318); however, V̇O2 was lower in each downhill trial (Δ = 1.6-2.2 mL·kg-1·min-1; d = 0.382-0.426). In the second bout, BLa was lower (p = 0.005, ηp2 = 0.602), RPE in the first trial was lower (p = 0.002; d = 0.923), and post exercise perceived soreness of the gastrocnemius, quadriceps, and hamstrings was attenuated (p < 0.002; ηp2 > 0.693). Perceived soreness of the gluteal muscles was lower in the second bout immediately post exercise, 24 h, and 48 h post exercise (p < 0.025; d > 0.922). A repeated bout of downhill running attenuated perceived muscle soreness and may modulate the physiological and perceived physical demand of a second bout of level and downhill running.

Cardiac repolarisation indices are associated with oxygen consumption during maximal exercise test in highly-trained cross-country skiers

ABSTRACT The objective of this study was to test the vectorelectrocardiographic T-wave characteristics for their associations with oxygen consumption (VO2) and physical performance during a maximal cardiopulmonary exercise test (CPET) in highly trained cross-country skiers. Male highly trained cross-country skiers (n = 30) performed the maximal CPET on the bicycle ergospirometric “Oxycon Pro” system with simultaneous oxygen consumption (VO2) and electrocardiogram recording. The measurements were done at rest; the stage preceding anaerobic threshold (preAnT); peak load; and recovery. The anaerobic threshold was estimated by respiratory exchange ratio. Physical performance was estimated by maximal oxygen consumption (VO2max/kg). VECG characteristics were calculated using Kors transformation procedure. During the test, the magnitudes of T-vector, Tx and Ty components decreased until preAnT, then stayed relatively stable until peak load, and reversed during recovery. In univariate linear regression analysis, T-vector amplitude and Tx, Ty and Tz magnitudes were associated with VO2/kg during the test (p < 0.010). The baseline T-vector characteristics were not associated with physical performance. At the preAnT stage, Tx and T-vector amplitude were associated with VO2max/kg (RC 12.70, 95% CI 0.68–24.73, p = 0.039 and RC 10.64, 95% CI 1.62–19.67, p = 0.023, respectively).

Glucose 6 phosphate dehydrogenase overexpression rescues the loss of cognition in the double transgenic APP/PS1 mouse model of Alzheimer’s disease

Mice models of Alzheimer's disease (APP/PS1) typically experience cognitive decline with age. G6PD overexpressing mice (G6PD-Tg) exhibit better protection from age-associated functional decline including improvements in metabolic and muscle functions as well as reduced frailty compared to their wild-type counterparts. Importantly G6PD-Tg mice show diminished accumulation of DNA oxidation in the brain at different ages in both males and females. To further explore the potential benefits of modulating the G6PD activity in neurodegenerative diseases, triple transgenic mice (3xTg G6PD) were generated, overexpressing APP, PSEN1, and G6PD genes. The cognitive decline characteristic of APP/PS1 mice was prevented in 3xTg G6PD mice, despite similar amyloid-β (Aβ) levels in the hippocampus. This challenges the dominant hypothesis in Alzheimer's disease (AD) etiology and the majority of therapeutic efforts in the field, based on the notion that Aβ is pivotal in cognitive preservation.Notably, the antioxidant properties of G6PD led to a decrease in oxidative stress parameters, such as improved GSH/GSSG and GSH/CysSSG ratios, without major changes in oxidative damage markers. Additionally, metabolic changes in 3xTg G6PD mice increased brain energy status, countering the hypometabolism observed in Alzheimer's models. Remarkably, a higher respiratory exchange ratio suggested increased carbohydrate utilization. The relative failures of Aβ-targeted clinical trials have raised significant skepticism on the amyloid cascade hypothesis and whether the development of Alzheimer's drugs has followed the correct path. Our findings highlight the significance of targeting glucose-metabolizing enzymes rather than solely focusing on Aβ in Alzheimer's research, advocating for a deeper exploration of glucose metabolism's role in cognitive preservation.

Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life.

Growth hormone-releasing hormone-deficient (GHRH-KO) mice have previously been characterized by lower body weight, disproportionately high body fat accumulation, preferential metabolism of lipids compared to carbohydrates, improved insulin sensitivity, and an extended lifespan. That these mice are long-lived and insulin-sensitive conflicts with the notion that adipose tissue accumulation drives the health detriments associated with obesity (i.e., diabetes), and indicates that GH signaling may be necessary for the development of adverse effects linked to obesity. This prompts investigation into the ultimate effect of diet-induced obesity on the lifespan of these long-lived mice. To this end, we initiated high-fat feeding in mid and late-life in GHRH-KO and wild-type (WT) mice. We carried out extensive lifespan analysis coupled with glucose/insulin tolerance testing and indirect calorimetry to gauge the metabolic effect of high-fat dietary stress through adulthood on these mice. We show that under high-fat diet (HFD) conditions, GHRH-KO mice display extended lifespans relative to WT controls. We also show that GHRH-KO mice are more insulin-sensitive and display less dramatic changes in their metabolism relative to WT mice, with GHRH-KO mice fed HFD displaying respiratory exchange ratios and glucose oxidation rates comparable to control-diet fed GHRH-KO mice, while WT mice fed HFD showed significant reductions in these parameters. Our results indicate that GH deficiency protects against the adverse effects of diet-induced obesity in later life.

Durability of Running Economy: Differences between Quantification Methods and Performance Status in Male Runners.

Running economy (RE) deteriorates during prolonged running, although the effect of measuring energy cost (EC) or oxygen cost (OC) on the magnitude of these changes has not been investigated. Similarly, it is unknown if runners' performance level may influence the deterioration of RE during prolonged running. The aims of this study were to compare changes in EC and OC measurements of RE during a prolonged run in a large cohort of well-trained male runners, and to compare changes between runners of high- and low-performance standard. Forty-four male runners (maximal oxygen uptake (V̇O 2max ) 62.4 mL·kg -1 ·min -1 ; 10-km time: 35:50 ± 4:40 mm:ss) completed an incremental test determining lactate threshold 1 (LT1) and V̇O 2max , and on a separate occasion, a 90-min run at LT1. Respiratory gases were collected at 15-min intervals. Subsequently, subgroups of high- (HP; 10-km time: 31:20 ± 01:00 mm:ss) and low-performing (LP; 10-km time: 41:50 ± 01:20 mm:ss) runners were compared. RE deterioration was only fractionally larger when expressed as OC than EC (0.1% greater from 30-90 min; P < 0.001), perhaps due to the small change in respiratory exchange ratio (-0.01) in this study. For the HP group, increases were lower than LP after 90 min in both EC (+2.3% vs +4.3%; P < 0.01) and OC (+2.4% vs +4.5%; P < 0.01). Similarly, at standardized distances, changes were lower for HP versus LP, for example, at 16.7 km + 1.0 versus +3.2% for EC ( P < 0.01), and +1.2 vs +3.4% for OC ( P < 0.001). The deterioration of RE was dependent on athlete's performance level, with HP runners displaying superior RE durability. The use of EC or OC had only a fractional influence on RE durability, although this may gain importance with larger shifts in substrate metabolism.

Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity

BackgroundIron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim...

Cadence Paradox in Cycling-Part 1: Maximal Lactate Steady State and Carbohydrate Utilization Dependent on Cycling Cadence.

To assess (1)whether and how a higher maximal lactate steady state (MLSS) at higher cycling cadence (RPM) comes along with higher absolute and/or fractional carbohydrate combustion (CHOMLSS), respectively, and (2)whether there is an interrelation between potential RPM-dependent MLSS effects and the maximally achievable RPM (RPMMAX). Twelve healthy males performed incremental load tests to determine peak power, peak oxygen uptake, and 30-minute MLSS tests at 50 and 100per minute, respectively, to assess RPM-dependent MLSS, corresponding power output, CHOMLSS responses, and 6-second sprints to measure RPMMAX. Peak power, peak carbon dioxide production, and power output at MLSS were lower (P = .000, ω2 = 0.922; P = .044, ω2 > 0.275; and P = .016, ω2 = 0.373) at 100per minute than at 50per minute. With 6.0 (1.5) versus 3.8 (1.2)mmol·L-1, MLSS was higher (P = .000, ω2 = 0.771) at 100per minute than at 50per minute. No corresponding RPM-dependent differences were found in oxygen uptake at MLSS, carbon dioxide production at MLSS, respiratory exchange ratio at MLSS, CHOMLSS, or fraction of oxygen uptake used for CHO at MLSS, respectively. There was no correlation between the RPM-dependent difference in MLSS and RPMMAX. The present study extends the previous finding of a consistently higher MLSS at higher RPM by indicating (1) that at fully established MLSS conditions, respiration and CHOMLSS management do not differ significantly between 100per minute and 50per minute, and (2)that linear correlation models did not identify linear interdependencies between RPM-dependent MLSS conditions and RPMMAX.

Effect of a high carbohydrate pre-exercise meal on metabolic and performance-related parameters in male athletes following two different strategies to improve fat utilization: An exploratory examination

The purpose of this additional examination of a larger intervention was to determine the effects of a carbohydrate-rich pre-exercise meal on metabolic and performance-related parameters in a group of male endurance athletes, who had previously followed either a high fat low carbohydrate (HFLC; n = 6) or high carbohydrate low glycaemic (LGI; n = 6) diet for 4 weeks. Participants continued their regular training routine during the intervention. Respiratory exchange ratio (RER), lactate concentrations ([La−]), substrate oxidation rates at rest and during a cycle ergometry with incremental workload were determined in the fasted state and 2 h after consuming a carbohydrate-rich (2 g per kg of body mass) pre-exercise meal. Power output at lactate thresholds, peak oxygen uptake (V̇O2peak), absolute and relative peak power during the incremental test were assessed. After consuming the pre-exercise meal, both groups showed increased levels of RER, [La−] and carbohydrate oxidation at rest and during the incremental test (p < 0.05; Cohen’s d > 0.8), and an improved V̇O2peak (p < 0.05; Cohen’s d > 0.5). Rm ANOVA revealed significant group differences in metabolic parameters. Despite meaningful baseline differences ([La−]: p = 0.133; ηp2 = 0.185; RER: p = 0.037; ηp2 = 0.367; carbohydrate oxidation: p = 0.041; ηp2 = 0.355) upregulation of carbohydrate metabolism was more pronounced in the LGI subgroup compared to the HFLC group after 4-weeks intervention, in both fasted ([La−]: p = 0.130; ηp2 = 0.214; RER: p = 0.001; ηp2 = 0.713; carbohydrate oxidation: p = 0.001; ηp2 =0.684) and postprandial states ([La−]: p = 0.036; ηp2 =0.369; RER: p = 0.001; ηp2 =0.705; carbohydrate oxidation: p = 0.001; ηp2 =0.665). Peak power during the final incremental test was slightly higher in the LGI subgroup compared with the HFLC subgroup (p = 0.320; ηp2 = 0.100). In this group of male endurance athletes, a LGI diet seemed to result in more favourable performance metrics as compared to a HFLC diet despite increases in carbohydrate availability before undertaking the performance test likely due to the ability to sustain higher workloads in training.

Aged microbiota exacerbates cardiac failure by PPARα/PGC1α pathway

The dysbiosis of gut microbiota with aging has been extensively studied, revealing its substantial contribution to variety of diseases. However, the impact of aged microbiota in heart failure (HF) remains unclear. In this study, we employed the method of fecal microbiota transplantation (FMT) from aged donors to investigate its role in the context of HF. Our results demonstrate that FMT from aged donors alters the recipient's gut microbiota composition and abundance. Furthermore, FMT impairs cardiac function and physical activity in HF mice. Aged FMT induces metabolic alterations, leading to body weight gain, impaired glucose tolerance, increased respiratory exchange ratio, and enhanced fat accumulation. The epicardium of aged FMT recipients shows fat accumulation, accompanied by cardiomyocyte hypertrophy, cardiac fibrosis and increased cellular apoptosis. Mechanistically, aged FMT suppresses the PPARα/PGC1α signaling pathway in HF. Notably, activation of PPARα effectively rescues the metabolic changes and myocardial injury caused by aged FMT. In conclusion, our study emphasizes the role of the PPARα/PGC1α signaling pathway in aged FMT-mediated HF.

Oxygen metabolism after cardiac arrest: Patterns and associations with survival

AimWhether changes in oxygen metabolism, as measured by oxygen consumption (VO2), carbon dioxide production (VCO2) and the respiratory exchange ratio (RER), are associated with survival after cardiac arrest is poorly understood. In this prospective observational study, we investigated the association between VO2, VCO2, and RER in the initial 12 and 24 h after return of spontaneous circulation (ROSC) and survival to hospital discharge. MethodsAdults with ROSC after cardiac arrest, admitted to the intensive care unit, requiring mechanical ventilation and treated with targeted temperature management were included. VO2 and VCO2 were measured continuously for 24 h after ROSC, using a noninvasive anesthesia monitor. Area under the curve for VO2, VCO2 & RER was calculated using all available values over 12 and 24 h after ROSC. Using logistic regression, we evaluated the relationship between these metabolic variables and survival to hospital discharge. Analyses were adjusted for temperature, vasopressors, and neuromuscular blockade. ResultsSixty four patients were included. Mean age was 64 ± 16 years, and 59% were women. There was no significant association between the area under the curve of VO2 or VCO2 and survival. A higher RER in the initial 12 h was associated with better survival (aOR = 3.97, 95% CI [1.01,15.6], p = 0.048). Survival was lower in those with median RER < 0.7 in the initial 12 h compared with those with a median RER ≥ 0.7 (25% vs 67%, p = 0.011). ConclusionHigher RER in the initial 12 h was associated with survival after cardiac arrest. The etiology of unusually low RERs in this patient population remains unclear.

Impact of MCT Oil and Caffeine on Substrate Metabolism during Submaximal Exercise

Introduction: Recent research has suggested that medium-chain triglyceride (MCT) supplementation may increase fat oxidation (FatOx) during aerobic exercise, sparing muscle glycogen and, perhaps, enhancing performance. As both MCT and caffeine (CAF) are theorized to elicit these effects, this pilot study’s purpose was to compare the physiological responses of their combined supplementation during submaximal cycling exercise. Methods: Eight aerobically trained males (mean±SD; age 23.6±4.4 years; body mass 82.3±15.8 kg; height 180.9±8.7 cm) completed one aerobic capacity (VO2peak) test and three 45-min exercise trials at 60% VO2peak. Blinded and counterbalanced, one-hour prior to each trial, participants consumed: MCT+CAF (20 mL + 100 mg), long-chain triglycerides (LCT)+CAF (40 mL + 100 mg), or CAF (100 mg). Oxygen consumption (VO2), carbon dioxide output (VCO2), and minute ventilation (VE) were measured, subsequently calculating respiratory exchange ratio (RER), energy expenditure (EE), carbohydrate oxidation (CarbOx), and FatOx. Results: No significant differences between conditions were observed for average VO2 (p=0.474; η2=0.101), VE (p=0.323; η2=0.149), (RER (p=0.323; η2=0.149), EE (p=0.474; η2=0.101), CarbOx (p=0.274; η2=0.169), or FatOx (p=0.478; η2=0.100) or for total EE (p=0.474; η2=0.101), CarbOx (p=0.274; η2=0.169), or FatOx (p=0.478; η2=0.100). Conclusions: Co-ingestion of MCT+CAF didn’t produce any significantly different physiological responses compared to co-ingestion of LCT+CAF or the CAF control.

Effect of Left Ventricular Diastolic Dysfunction on the Cardiopulmonary Exercise Test in Patients With Cardiovascular Disease

Left ventricular diastolic dysfunction exists in patients with heart failure with reduced ejection fraction and causes activity restriction and a poor prognosis, but there have been few reports about exercise tolerance in patients with diastolic dysfunction, regardless of left ventricular ejection fraction (LVEF). In this study, 294 cardiovascular disease patients who performed a cardiopulmonary exercise test (CPX) with an adequate examination by echocardiography at Fukuoka University Hospital from 2011 to 2020 were investigated. Patients were divided into groups with grade I and grade II or III diastolic dysfunction according to diagnostic criteria, regardless of LVEF, by echocardiography. After adjusting for age, gender, body mass index, smoking, and LVEF by propensity score matching, we compared the results of CPX between the grade I and grade II/III groups. There were no significant differences in hemodynamic parameters, or in the respiratory exchange ratio, oxygen uptake per body weight, oxygen uptake per heart rate, or parameters of ventilatory volume. Ventilatory equivalents per oxygen uptake and per carbon dioxide output were significantly worse in the grade II/III group from the rest to peak periods during CPX. In conclusion, left ventricular diastolic dysfunction worsens ventilatory efficacy during CPX. This effect potentially contributes to a poor prognosis in left ventricular diastolic dysfunction.

Sex Differences In Energy Expenditure, Metabolic Heat, And Substrate Utilization During Exercise-Heat Stress

Purpose: To understand the influence of repeated heat exposures and biological sex on metabolic outcomes surrounding heat acclimation (HA). Based on previous data, we hypothesized that repeated heat exposures would result in higher resting caloric expenditure and exercising metabolic heat production in men (vs. women). Methods: Twenty participants (65% men, 22±3 yrs, 70.1±13.7 kg, VO2max 49.9±6.8 mL·kg −1·min −1) had 8 daily exercise-heat sessions (40°C, 40%rh, at least 60min) including heat tolerance tests (HTT; 120 min, 3.1 mph, 2% grade) on days 1 and 8. Resting energy expenditure (REE) and respiratory exchange ratio (RER) were assessed pre- and post-HTT on days 1 and 8. Metabolic heat production (MHP) and RER were collected during the HTT. Data are presented as mean difference (MD) (95% confidence intervals). For REE and RER, a 2x2 ANOVA compared metrics before HTT vs. after HTT session, pre-HA vs. post HA with sex as a between-subjects factor. For MHP and RER during exercise, a dependent samples t-test compared pre-HA vs. post-HA and independent samples t-test compared sexes pre-HA vs. post-HA. Results: Pre-HA: RER was higher before vs. after the HTT (MD:0.07 (0.05,0.09) A.U., p&lt;0.001) overall with no difference between sexes. REE was not different before vs. after the HTT (p&gt;0.05) overall, but males had higher REE before HTT (MD:564 (291,836) kcal·day −1, p&lt;0.001) and after HTT (MD:666 (395,938) kcal·day −1, p&lt;0.001) than women. Post-HA: RER was higher before vs. after the HTT (MD:0.08 (0.06,0.10) A.U., p&lt;0.001) overall with no difference between sexes. REE was not different before vs. after the HTT (p&gt;0.05), but males had higher REE before (MD:581 (328,834) kcal·day −1, p&lt;0.001) and after HTT (MD:617 (411,823) kcal·day −1, p&lt;0.001) compared to women. Comparing HA Status: RER was not different between HA status before or after the HTT (p&gt;0.05). REE was not different between HA status before the HTT (p&gt;0.05). After HTT, REE was greater pre-HA compared to post-HA (MD:142 (26,259) kcal·day −1, p=0.019). During activity, MHP was greater pre-HA compared to post-HA (MD:14 (-2,31) W/m2, p=0.042); RER was not different (p&gt;0.05). Pre-HA there were no differences in MHP or RER between sexes (p&gt;0.05); post-HA, men had greater MHP than women (MD:36 (3,67) W/m2, p=0.016); there were no sex differences in RER. Conclusion: Men exhibited greater REE than women at each time point under both conditions and men produced more metabolic heat following HA. In response to completing 8 heat exposures as part of a HA protocol, men and women differed in caloric expenditure and MHP, but not in substrate utilization. Thus, our findings provide supporting evidence for sex-specific nutritional recommendations surrounding exercise-heat stress. Funding Source: DoD BA200299. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.