The biphasic activity of autophagy and heat shock protein response in peripheral blood mononuclear cells following acute resistance exercise in resistance-trained males.

PURPOSE: Autophagy and heat shock protein (HSP) response are proteostatic systems involved in the acute and adaptive responses to exercise. These systems may upregulate sequentially following cellular stress including acute exercise, however, currently few data exist in humans. This study investigated the autophagic and HSP responses to acute intense lower body resistance exercise in peripheral blood mononuclear cells (PBMCs) with and without branched-chain amino acids (BCAA) supplementation. METHODS: Twenty resistance-trained males (22.3 ± 1.5 yr; 175.4 ± .7 cm; 86.4 ± 15.6 kg) performed about of intense lower body resistance exercise and markers of autophagy and HSP70 were measured immediately post- (IPE) and 2, 4, 24, 48, and 72 h post-exercise. Prior to resistance exercise, 10 subjects were randomly assigned to BCAA supplementation of 0.22 g/kg/d for 5 days pre-exercise and up to 72 h following exercise while the other 10 subjects consumed a placebo (PLCB). RESULTS: There were no difference in autophagy markers or HSP70 expression between BCAA and PLCB groups. LC3II protein expression was significantly lower 2 and 4 h post-exercise compared to pre-exercise. LC3II: I ratio was not different at any time point compared to pre-exercise. Protein expression of p62 was lower IPE, 2, and 4 h post-exercise and elevated 24 h post-exercise. HSP70 expression was elevated 48 and 72 h post-exercise. CONCLUSIONS: Autophagy and HSP70 are upregulated in PBMCs following intense resistance exercise with autophagy increasing initially post-exercise and HSP response in the latter period. Moreover, BCAA supplementation did not affect this response.

Ultraprocessed, hyper-palatable, and high energy density foods: Prevalence and distinction across 30 years in the United States.

OBJECTIVE: Ultraprocessed foods (UPF), hyper-palatable foods (HPF), and high energy density (HED) foods may contribute to obesity risk. All have distinct definitions; however, it is unknown the degree to which they may identify overlapping or distinct foods. This study examined the availability of UPF, HPF, and HED foods in the US food system from 1988 to 2018 and the degree of distinction across definitions. METHODS: Four data sets representing the US food system (1988, 2001, 2006, 2018) from the US Department of Agriculture were analyzed. UPF were identified based on the extent of industrialized processing. HPF were identified using the standardized definition that specifies palatability-inducing nutrient combinations. HED was characterized as >2.0 kcal/g. RESULTS: Across years, 58% to 65% of foods were classified as UPF, 55% to 69% as HPF, and 37% to 47% as HED. Prevalence of UPF, HPF, and HED foods was higher in 2018 versus 1988 (p values < 0.001); HPF evidenced the largest increase (14%) and UPF evidenced the smallest (4%) over time. There was moderate to high overlap in foods (40%-70%) across definitions. CONCLUSIONS: Together, UPF, HPF, and HED foods comprise most foods in the US food supply. Changes in availability varied across definitions, with substantial increases in HPF and HED and relative stability of UPF.

Certainty of Evidence Assessment in Systematic Reviews Published by High-Impact Sports Science Journals: A Meta-epidemiological Study.

BACKGROUND: Assessing certainty of evidence is a key element of any systematic review. The aim of this meta-epidemiology study was to understand the frequency and ways with which certainty of evidence is assessed in contemporary systematic reviews published in high-impact sports science journals. METHODS: We searched PubMed and relevant journal web sites from 1 August 2016 to 11 October 2022 for systematic reviews published in the top-ten highest-impact journals within the 2020 Journal Citation Report for the Sports Sciences category. Pairs of independent reviewers screened items using a priori established criteria. RESULTS: Of 1250 eligible documents, 258 (20.6%) assessed the certainty of evidence, defined as using two or more distinct domains to provide an overall rating of the trustworthiness of findings across studies. Nine methods were cited for assessing certainty, with the most common being the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach (61.6%). The proportion of systematic reviews assessing certainty of evidence appeared to increase over the 6-year timeframe analyzed. Across all reviews analyzed, a large majority addressed the domains of risk of bias, imprecision, and inconsistency of the results. Other certainty domains including indirectness/applicability were less commonly assessed. DISCUSSION: Only one in five recent contemporary systematic reviews in the field of exercise and sports science assessed certainty of evidence. Organizational and institutional education on methods for assessing evidence may help further increase uptake of these methods and improve both the quality and clinical impact of systematic reviews in the field.

No Effect of Breakfast Consumption Observed for Afternoon Resistance Training Performance in Habitual Breakfast Consumers and Nonconsumers: A Randomized Crossover Trial.

BACKGROUND: Pre-exercise meal frequency is commonly believed to impact exercise performance, but little is known about its impact on resistance training. OBJECTIVE: This study investigated the impact of breakfast consumption on afternoon resistance training performance in habitual breakfast consumers and nonconsumers. DESIGN: A randomized, crossover study was conducted in Lubbock, TX between November 2021 and May 2022. PARTICIPANTS: Thirty-nine resistance-trained male (n = 20) and female (n = 19) adults (mean ± SD age 23.0 ± 4.7 years) who habitually consumed (≥5 d/wk; n = 19) or did not consume (≥5 d/wk; n = 20) breakfast completed the study. INTERVENTION: After the establishment of 1-repetition maximums at the first visit, participants completed 2 additional visits, each of which included 4 sets of barbell back squat, bench press, and deadlift, using 80% of their 1-repetition maximum after either consuming breakfast and lunch or the same food at lunch only. MAIN OUTCOME MEASURES: Repetitions, along with average and peak average concentric velocity and power, were measured for all repetitions throughout each exercise session. Visual analog scales were used to assess feelings of fatigue, energy, focus, hunger, desire to eat, and fullness throughout each exercise session. STATISTICAL ANALYSES PERFORMED: Data were analyzed using linear mixed-effects models. RESULTS: No interactions or main effects involving condition or habitual breakfast consumption were observed for resistance training outcomes, although sex differences were noted. Male participants performed significantly fewer repetitions on sets 2, 3, and 4 (P < .014) for total repetitions, on sets 2 and 4 for barbell back squat (P < .023), and set 4 for deadlift (P = .006), with no observed differences between sexes for bench press repetitions. Male participants displayed reductions in average power across all sets and exercises except deadlift. CONCLUSIONS: These data suggest that alterations in pre-exercise meal frequency may not influence afternoon resistance training performance provided similar total nutritional intake is consumed.

Evaluation of novel beverage formulations for hydration enhancement in humans.

This study evaluated the influence of novel beverage formulations on bioimpedance- and urine-based hydration markers. Thirty young healthy adults (n=16 females, n=14 males; age: 23.2±3.7 years; BMI: 24.3±3.3 kg/m2) participated in a randomized, double-blind, placebo-controlled, crossover study. Participants completed three conditions with baseline bioimpedance, urine, and body mass assessments, followed by ingestion of one liter of a test beverage over a 30-minute period. The three beverages were: active hydration formulation in still (AFstill) or sparkling (AFspark) water and a still water control. The active formulations were identical in concentrations of alpha-cyclodextrin and complexing agents. Following beverage ingestion, bioimpedance assessments were performed every 15 minutes for two hours, followed by final urinary and body mass assessments. The primary bioimpedance outcomes were phase angle at 50 kHz, resistance of the extra-cellular compartment (R0), and resistance of the intracellular compartment (Ri). Data were analyzed using linear mixed effects models, Friedman tests, and Wilcoxon tests. Statistically significant changes in phase angle values were observed at 30 (p=0.004) and 45 minutes (p=0.024) following the initiation of beverage ingestion in the AFstill condition as compared to the reference model (i.e., control condition at baseline). Although differences between conditions were not statistically significant at later time points, the data were consistent with AFstill having greater elevations in phase angle throughout the monitoring period. At the 30-minute time point only, statistically significant differences in R0 for AFspark (p<0.001) and in Ri for AFstill (p=0.008) were observed. When averaged across post-ingestion time points, there was a trend (p=0.08) for Ri differences between conditions. The net fluid balance was greater than zero, indicating retention of ingested fluid, for AFstill (p=0.02) and control (p=0.03), with a trend for AFspark (p=0.06). In conclusion, an active formulation containing alpha-cyclodextrin in still water demonstrated potential benefits for enhancing hydration markers in humans.

Protracted CLN3 Batten disease in mice that genetically model an exon-skipping therapeutic approach.

Genetic mutations that disrupt open reading frames and cause translation termination are frequent causes of human disease and are difficult to treat due to protein truncation and mRNA degradation by nonsense-mediated decay, leaving few options for traditional drug targeting. Splice-switching antisense oligonucleotides offer a potential therapeutic solution for diseases caused by disrupted open reading frames by inducing exon skipping to correct the open reading frame. We have recently reported on an exon-skipping antisense oligonucleotide that has a therapeutic effect in a mouse model of CLN3 Batten disease, a fatal pediatric lysosomal storage disease. To validate this therapeutic approach, we generated a mouse model that constitutively expresses the Cln3 spliced isoform induced by the antisense molecule. Behavioral and pathological analyses of these mice demonstrate a less severe phenotype compared with the CLN3 disease mouse model, providing evidence that antisense oligonucleotide-induced exon skipping can have therapeutic efficacy in treating CLN3 Batten disease. This model highlights how protein engineering through RNA splicing modulation can be an effective therapeutic approach.

Anthropometric Predictors of Conventional Deadlift Kinematics and Kinetics: A Preliminary Study.

The purpose of this preliminary analysis was to determine if there are relationships between anthropometric characteristics (arm length, torso length, thigh length, and shank length) and conventional deadlift (CDL) kinematics and kinetics during a 5 sets of 5 repetitions (5 × 5) CDL routine in resistance-trained males. Eleven males who had experience with the deadlift exercise were included in this analysis (age: 21.5 ± 1.4 y; height: 180.7 ± 5.7 cm; body mass: 89.9 ± 16.0 kg). Anthropometrics were measured by a 3-dimensional optical scanner. The participants underwent a 5 × 5 CDL workout using a self-selected load corresponding to a rating of perceived exertion (RPE) of 8 out of 10. Performance outcomes were measured synchronously using a 3-dimensional 12-camera motion capture system and two force platforms. Outcomes were averaged across all sets and analyzed using multiple linear regression. The selected anthropometric variables were not significantly related to the CDL performance outcomes, except for concentric ankle work. However, in the overall model, anthropometric predictors did not significantly predict ankle concentric work (p = 0.11; R 2 = 0.67; R_2adj = 0.45). Independently, thigh length significantly correlated with ankle concentric work (p = 0.03). In this model, thigh length accounted for 55% of the normalized variance in ankle concentric work. The results from this preliminary study suggest that arm length, torso length, and shank length may not play a clear role in the examined CDL outcomes, but thigh length may be positively correlated with ankle concentric work during a 5 × 5 CDL routine in resistance-trained males.

Sexual dimorphism in bidirectional SR-mitochondria crosstalk in ventricular cardiomyocytes.

Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca2+ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca2+] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca2+ accumulation, thereby reducing ROS production and stress-induced intracellular Ca2+ mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-[Ca2+] in female rat VCMs challenged with ß-adrenergic agonist isoproterenol compared to males. Biochemical studies revealed decreased mitochondria Ca2+ uniporter expression and increased supercomplex assembly in rat and human female ventricular tissues vs male. Importantly, western blot analysis showed higher expression levels of COX7RP, an estrogen-dependent supercomplex assembly factor in female heart tissues vs males. Furthermore, COX7RP was decreased in hearts from aged and ovariectomized female rats. COX7RP overexpression in male VCMs increased mitochondrial supercomplexes, reduced mito-ROS and spontaneous SR Ca2+ release in response to ISO. Conversely, shRNA-mediated knockdown of COX7RP in female VCMs reduced supercomplexes and increased mito-ROS, promoting intracellular Ca2+ mishandling. Compared to males, mitochondria in female VCMs exhibit higher ETC subunit incorporation into supercomplexes, supporting more efficient electron transport. Such organization coupled to lower levels of mito-[Ca2+] limits mito-ROS under stress conditions and lowers propensity to pro-arrhythmic spontaneous SR Ca2+ release. We conclude that sexual dimorphism in mito-Ca2+ handling and ETC organization may contribute to cardioprotection in healthy premenopausal females.

Effects of a ready-to-drink thermogenic beverage on resting energy expenditure, hemodynamic function, and subjective outcomes.

BACKGROUND: Thermogenic supplements are often consumed by individuals seeking to improve energy levels and reduce body fat. These supplements are sold in powdered or ready-to-drink (RTD) forms and consist of a blend of ingredients such as caffeine, green tea extract, and other botanical compounds. While there is evidence that thermogenic supplements can positively affect resting energy expenditure (REE), the effect varies based on the combination of active ingredients. Additionally, there is some concern that thermogenic supplements may cause unwanted side effects on hemodynamic variables, like heart rate (HR) and blood pressure (BP). Therefore, further investigation into the efficacy and safety of commercially available products is warranted. METHODS: Twenty-eight individuals (14 F, 14 M; age: 23.3 ± 3.9 yrs; height: 169.4 ± 8.6 cm; body mass: 73.3 ± 13.1 kg) completed two visits in a randomized, double-blind, crossover fashion. Each visit began with baseline REE, HR, and BP assessments, which were followed by ingestion of an active RTD thermogenic beverage (RTD; OxyShred Ultra Energy) or placebo (PL). Assessments were repeated at the intervals of 35-50- and 85-100-minutes post-ingestion. In addition, subjective outcomes of energy, focus, concentration, alertness, and mood were collected five times throughout each visit. Repeated-measures analysis of variance was performed with condition and time specified as within-subjects factors and sex and resistance training (RT) status as between-subjects factors. Statistical significance was accepted at p < 0.05. RESULTS: A significant condition × time interaction was observed for REE (p < 0.001). Higher REE values were demonstrated at 35-50 min (0.08 ± 0.02 kcal/min; p = 0.001; 5.2% difference) and 85-100 min (0.08 ± 0.02 kcal/min; p = 0.001; 5.5% difference) after RTD ingestion as compared to PL. No significant condition × time interactions were observed for respiratory quotient, HR, or BP. Condition main effects indicated lower HR (3.0 ± 0.9 bpm; p = 0.003), higher SBP (3.5 ± 1.1 mm Hg; p = 0.003) and higher DBP (3.5 ± 0.9 mm Hg; p < 0.001) in RTD as compared to PL, irrespective of time. Condition × time interactions were observed for all subjective outcomes (p ≤ 0.02). Post hoc tests indicated statistically significant benefits of the RTD over PL for energy, focus, concentration, and alertness, without significant differences for mood after correction for multiple comparisons. Sex and RT status were not involved in interactions for any outcomes, except for a Sex × RT status interaction for energy, indicating higher energy ratings in non-resistance-trained vs. resistance-trained males. CONCLUSIONS: These data suggest that acute ingestion of a thermogenic RTD beverage significantly increases REE, and this elevated caloric expenditure is sustained for at least 100 minutes following ingestion. Furthermore, the RTD beverage increased measures of energy, focus, concentration, and alertness as compared to placebo. While minor differences in hemodynamic variables were observed between conditions, all values stayed within normal ranges. Individuals aiming to increase energy expenditure may benefit from acute ingestion of an RTD thermogenic supplement.

Assessing the reliability and cross-sectional and longitudinal validity of fifteen bioelectrical impedance analysis devices.

The purpose of this investigation was to expand upon the limited existing research examining the test-retest reliability, cross-sectional validity and longitudinal validity of a sample of bioelectrical impedance analysis (BIA) devices as compared with a laboratory four-compartment (4C) model. Seventy-three healthy participants aged 19-50 years were assessed by each of fifteen BIA devices, with resulting body fat percentage estimates compared with a 4C model utilising air displacement plethysmography, dual-energy X-ray absorptiometry and bioimpedance spectroscopy. A subset of thirty-seven participants returned for a second visit 12-16 weeks later and were included in an analysis of longitudinal validity. The sample of devices included fourteen consumer-grade and one research-grade model in a variety of configurations: hand-to-hand, foot-to-foot and bilateral hand-to-foot (octapolar). BIA devices demonstrated high reliability, with precision error ranging from 0·0 to 0·49 %. Cross-sectional validity varied, with constant error relative to the 4C model ranging from -3·5 (sd 4·1) % to 11·7 (sd 4·7) %, standard error of the estimate values of 3·1-7·5 % and Lin's concordance correlation coefficients (CCC) of 0·48-0·94. For longitudinal validity, constant error ranged from -0·4 (sd 2·1) % to 1·3 (sd 2·7) %, with standard error of the estimate values of 1·7-2·6 % and Lin's CCC of 0·37-0·78. While performance varied widely across the sample investigated, select models of BIA devices (particularly octapolar and select foot-to-foot devices) may hold potential utility for the tracking of body composition over time, particularly in contexts in which the purchase or use of a research-grade device is infeasible.

mt-tRNAs in the polymerase gamma mutant heart.

Introduction: Mice harboring a D257A mutation in the proofreading domain of the mitochondrial DNA polymerase, Polymerase Gamma (POLG), experience severe metabolic dysfunction and display hallmarks of accelerated aging. We previously reported a mitochondrial unfolded protein response (UPTmt) - like (UPRmt-like) gene and protein expression pattern in the right ventricular tissue of POLG mutant mice. Aim: We sought to determine if POLG mutation altered the expression of genes encoded by the mitochondria in a way that might also reduce proteotoxic stress. Methods and Results: The expression of genes encoded by the mitochondrial DNA was interrogated via RNA-seq and northern blot analysis. A striking, location-dependent effect was seen in the expression of mitochondrial-encoded tRNAs in the POLG mutant as assayed by RNA-seq. These expression changes were negatively correlated with the tRNA partner amino acid's amyloidogenic potential. Direct measurement by northern blot was conducted on candidate mt-tRNAs identified from the RNA-seq. This analysis confirmed reduced expression of MT-TY in the POLG mutant but failed to show increased expression of MT-TP, which was dramatically increased in the RNA-seq data. Conclusion: We conclude that reduced expression of amyloid-associated mt-tRNAs is another indication of adaptive response to severe mitochondrial dysfunction in the POLG mutant. Incongruence between RNA-seq and northern blot measurement of MT-TP expression points towards the existence of mt-tRNA post-transcriptional modification regulation in the POLG mutant that alters either polyA capture or cDNA synthesis in RNA-seq library generation. Together, these data suggest that 1) evolution has distributed mt-tRNAs across the circular mitochondrial genome to allow chromosomal location-dependent mt-tRNA regulation (either by expression or PTM) and 2) this regulation is cognizant of the tRNA partner amino acid's amyloidogenic properties.

Liposomal Mineral Absorption: A Randomized Crossover Trial.

Multivitamin/mineral (MVM) supplements are one of the most popular dietary supplement categories. The purpose of this analysis was to determine if a novel liposomal delivery mechanism improves mineral absorption from an MVM product. In a randomized crossover trial, 25 healthy participants (12 females, 13 males) completed two testing sessions in which blood samples were collected at baseline and 2, 4, and 6 h following the ingestion of either a liposomal MVM or a nutrient-matched standard MVM. Analysis of MVM products indicated an elemental iron content of 9.4 and 10.1 mg (~50% U.S. FDA Daily Value) and an elemental magnesium content of 22.0 and 23.3 mg (~5% U.S. FDA Daily Value) in the liposomal and standard MVM products, respectively. Blood samples were analyzed for concentrations of iron and magnesium using colorimetric assays. Changes in mineral concentrations were analyzed using linear mixed models, and pharmacokinetic parameters were compared between conditions. For iron, statistically significant condition × time interactions were observed for percent change from baseline (p = 0.002), rank of percent change from baseline (p = 0.01), and raw concentrations (p = 0.02). Follow-up testing indicated that the liposomal condition exhibited larger changes from baseline than the standard MVM condition at 4 (p = 0.0001; +14.3 ± 18.5% vs. -6.0 ± 13.1%) and 6 h (p = 0.0002; +1.0 ± 20.9% vs. -21.0 ± 15.3%) following MVM ingestion. These changes were further supported by a 50% greater mean incremental area under the curve in the liposomal condition (33.2 ± 30.9 vs. 19.8 ± 19.8 mcg/dL × 6 h; p = 0.02, Cohen's d effect size = 0.52). In contrast, no differential effects for magnesium absorption were observed. In conclusion, iron absorption from an MVM product is enhanced by a liposomal delivery mechanism.

Influence of Acute Water Ingestion and Prolonged Standing on Raw Bioimpedance and Subsequent Body Fluid and Composition Estimates.

This study evaluated the influence of acute water ingestion and maintaining an upright posture on raw bioimpedance and subsequent estimates of body fluids and composition. Twenty healthy adults participated in a randomized crossover study. In both conditions, an overnight food and fluid fast was followed by an initial multi-frequency bioimpedance assessment (InBody 770). Participants then ingested 11 mL/kg of water (water condition) or did not (control condition) during a 5-minute period. Thereafter, bioimpedance assessments were performed every 10 minutes for one hour with participants remaining upright throughout. Linear mixed effects models were used to examine the influence of condition and time on raw bioimpedance, body fluids, and body composition. Water consumption increased impedance of the arms but not trunk or legs. However, drift in leg impedance was observed, with decreasing values over time in both conditions. No effects of condition on body fluids were detected, but total body water and intracellular water decreased by ~0.5 kg over time in both conditions. Correspondingly, lean body mass did not differ between conditions but decreased over the measurement duration. The increase in body mass in the water condition was detected exclusively as fat mass, with final fat mass values ~1.3 kg higher than baseline and also higher than the control condition. Acute water ingestion and prolonged standing exert practically meaningful effects on relevant bioimpedance variables quantified by a modern, vertical multi-frequency analyzer. These findings have implications for pre-assessment standardization, methodological reporting, and interpretation of assessments.

Estrogen Receptor-ß Agonists Modulate T-Lymphocyte Activation and Ameliorate Left Ventricular Remodeling During Chronic Heart Failure.

BACKGROUND: CD4+ T cells temporally transition from protective to pathological during ischemic heart failure (HF; 8 weeks postmyocardial infarction). Cellular mechanisms mediating this shift are unknown. METHODS: RNA-sequencing of cardiac CD4+ T cells and flow cytometric analysis of immune cells was conducted. RESULTS: RNA-sequencing of CD4+ T cells from the failing hearts of male mice indicated activation of ER (estrogen receptor)-α signaling. Flow cytometric analysis showed that ERα in CD4+ T cells decreases significantly at 3-day postmyocardial infarction but increases during HF. To antagonize ERα, we tested a novel ERß agonist (OSU-ERb-012) to inhibit T cells and blunt left ventricular remodeling. Proliferation assays showed that OSU-ERb-012 dose-dependently inhibited proliferation and proinflammatory cytokine expression in anti-CD3/CD28 stimulated splenic T cells isolated from both the sexes. For in vivo efficacy, 10- to 12-week-old male and ovariectomized female mice were randomized at 4 weeks postmyocardial infarction and treated with either vehicle or drug (60 mg/kg per day; oral). While vehicle-treated HF mice displayed progressive left ventricular dilatation with significantly increased end-systolic and end-diastolic volumes from 4 to 8 weeks postmyocardial infarction, treatment with OSU-ERb-012 significantly blunted these changes and stopped left ventricular remodeling in both the sexes. Reduction in tibia-normalized heart and left ventricular weights, cardiomyocyte hypertrophy and interstitial fibrosis further supported these results. Additionally, OSU-ERb-012 treatment selectively inhibited cardiac, splenic, and circulating CD4+ T cells without affecting other myeloid and lymphoid cells in the HF mice. CONCLUSIONS: Our studies indicate that ERß agonists and OSU-ERb-012, in particular, could be used as selective immunomodulatory drugs to inhibit CD4+ T cells during chronic HF.

The influence of caffeinated and non-caffeinated multi-ingredient pre-workout supplements on resistance exercise performance and subjective outcomes.

Background: There is substantial consumer and practitioner interest in an emerging supplement class known as multi-ingredient pre-workout supplements (MIPS), largely due to their prevalence in resistance training communities as well as research findings demonstrating the ergogenic impact of caffeine on muscular performance. However, limited research has examined the potential efficacy of non-caffeinated MIPS, despite their growing popularity among those who are caffeine-sensitive or who train later in the day. Methods: Twenty-four resistance-trained college-aged males (n = 12) and females (n = 12) completed three visits in which they ingested either a caffeinated MIPS (C), an otherwise identical non-caffeinated MIPS (NC), or placebo in a double-blind, counterbalanced, crossover fashion. Squat isometric peak force (PFiso), rate of force development (RFD), and isokinetic performance were assessed. Upper and lower body maximal muscular strength and endurance were evaluated using the bench press and leg press, respectively. Visual analog scales for energy, focus, and fatigue were completed five times throughout the testing protocol. The effects of supplementation and biological sex on all variables were examined using linear mixed effects models. Results: Significantly greater PFiso was observed in both C (b: 0.36 transformed units [0.09, 0.62]) and NC (b: 0.32 transformed units [95% CI: 0.05, 0.58]) conditions, relative to placebo. Early RFD (RFD50) may have been higher with supplementation, particularly in females, with no effects for late RFD (RFD200) or peak RFD. In addition, increases in subjective energy after supplement ingestion were noted for C, but not NC. No effects of supplementation on traditional resistance exercise performance or isokinetic squat performance were observed, other than a lower leg press one-repetition maximum for males in the NC condition. Conclusions: These data indicate that acute ingestion of either a caffeinated or non-caffeinated pre-workout formulation improved maximal force production during an isometric squat test but did not provide additional benefit to leg press, bench press, or isokinetic squat performance over placebo, within the context of a laboratory environment. The consumption of a caffeinated, but not non-caffeinated, MIPS increased subjective ratings of energy over placebo when assessed as part of a testing battery.

Molecular signature of cardiac remodeling associated with Polymerase Gamma mutation.

AIMS: Metabolic function/dysfunction is central to aging biology. This is well illustrated by the Polymerase Gamma (POLG) mutant mouse where a key residue of the mitochondrial DNA polymerase is mutated (D257A), causing loss of mitochondrial DNA stability and dramatically accelerated aging processes. Given known cardiac phenotypes in the POLG mutant, we sought to characterize the course of cardiac dysfunction in the POLG mutant to guide future intervention studies. MATERIALS AND METHODS: Cardiac echocardiography and terminal hemodynamic analyses were used to define the course of dysfunction in the right and left cardiac ventricles in the POLG mutant. We also conducted RNA-seq analysis on cardiac right ventricles to identify mechanisms engaged by severe metabolic dysfunction and compared this analysis to several publically available datasets. KEY FINDINGS: Interesting sex differences were noted as female POLG mutants died earlier than male POLG mutants and LV chamber diameters were impacted earlier in females than males. Moreover, male mutants showed LV wall thinning while female mutant LV walls were thicker. Both males and females displayed significant RV hypertrophy. POLG mutants displayed a gene expression pattern associated with inflammation, fibrosis, and heart failure. Finally, comparative omics analyses of publically available data provide additional mechanistic and therapeutic insights. SIGNIFICANCE: Aging-associated cardiac dysfunction is a growing clinical problem. This work uncovers sex-specific cardiac responses to severe metabolic dysfunction that are reminiscent of patterns seen in human heart failure and provides insights to the molecular mechanisms engaged downstream of severe metabolic dysfunction that warrant further investigation.

Physiological responses to acute fasting: implications for intermittent fasting programs.

Intermittent fasting (IF) is a dietary strategy that involves alternating periods of abstention from calorie consumption with periods of ad libitum food intake. There is significant interest in the body of literature describing longitudinal adaptations to IF. Less attention has been given to the acute physiological responses that occur during the fasting durations that are commonly employed by IF practitioners. Thus, the purpose of this review was to examine the physiological responses - including alterations in substrate metabolism, systemic hormones, and autophagy - that occur throughout an acute fast. Literature searches were performed to locate relevant research describing physiological responses to acute fasting and short-term starvation. A single fast demonstrated the ability to alter glucose and lipid metabolism within the initial 24 hours, but variations in protein metabolism appeared to be minimal within this time frame. The ability of an acute fast to elicit significant increases in autophagy is still unknown. The information summarized in this review can be used to help contextualize existing research and better inform development of future IF interventions.

Comparison of Indirect Calorimetry and Common Prediction Equations for Evaluating Changes in Resting Metabolic Rate Induced by Resistance Training and a Hypercaloric Diet.

ABSTRACT: Rodriguez, C, Harty, PS, Stratton, MT, Siedler, MR, Smith, RW, Johnson, BA, Dellinger, JR, Williams, AD, White, SJ, Benavides, ML, and Tinsley, GM. Comparison of indirect calorimetry and common prediction equations for evaluating changes in resting metabolic rate induced by resistance training and a hypercaloric diet. J Strength Cond Res 36(11): 3093-3104, 2022-The ability to accurately identify resting metabolic rate (RMR) changes over time allows practitioners to prescribe appropriate adjustments to nutritional intake. However, there is a lack of data concerning the longitudinal utility of commonly used RMR prediction equations. The purpose of this study was to evaluate the validity of several commonly used prediction equations to track RMR changes during a hypercaloric nutritional intervention and supervised resistance exercise training program. Twenty resistance-trained men completed the study. The protocol lasted 6 weeks, and subjects underwent RMR assessments by indirect calorimetry (IC) preintervention and postintervention to obtain reference values. Existing RMR prediction equations based on body mass (BM) or dual-energy X-ray absorptiometry fat-free mass (FFM) were also evaluated. Equivalence testing was used to evaluate whether each prediction equation demonstrated equivalence with IC. Null hypothesis significance testing was also performed, and Bland-Altman analysis was used alongside linear regression to assess the degree of proportional bias. Body mass and FFM increased by 3.6 ± 1.7 kg and 2.4 ± 1.6 kg, respectively. Indirect calorimetry RMR increased by 165 ± 97 kcal·d -1 , and RMR:FFM increased by 5.6 ± 5.2%. All prediction equations underestimated mean RMR changes relative to IC, with magnitudes ranging from 75 to 155 kcal·d -1 , while also displaying unacceptable levels of negative proportional bias. In addition, no equation demonstrated equivalence with IC. Common RMR prediction equations based on BM or FFM did not fully detect the increase in RMR observed with resistance training plus a hypercaloric diet. Overall, the evaluated prediction equations are unsuitable for estimating RMR changes in the context of this study.

Tracking changes in body composition: comparison of methods and influence of pre-assessment standardisation.

The present study reports the validity of multiple assessment methods for tracking changes in body composition over time and quantifies the influence of unstandardised pre-assessment procedures. Resistance-trained males underwent 6 weeks of structured resistance training alongside a hyperenergetic diet, with four total body composition evaluations. Pre-intervention, body composition was estimated in standardised (i.e. overnight fasted and rested) and unstandardised (i.e. no control over pre-assessment activities) conditions within a single day. The same assessments were repeated post-intervention, and body composition changes were estimated from all possible combinations of pre-intervention and post-intervention data. Assessment methods included dual-energy X-ray absorptiometry (DXA), air displacement plethysmography, three-dimensional optical imaging, single- and multi-frequency bioelectrical impedance analysis, bioimpedance spectroscopy and multi-component models. Data were analysed using equivalence testing, Bland-Altman analysis, Friedman tests and validity metrics. Most methods demonstrated meaningful errors when unstandardised conditions were present pre- and/or post-intervention, resulting in blunted or exaggerated changes relative to true body composition changes. However, some methods - particularly DXA and select digital anthropometry techniques - were more robust to a lack of standardisation. In standardised conditions, methods exhibiting the highest overall agreement with the four-component model were other multi-component models, select bioimpedance technologies, DXA and select digital anthropometry techniques. Although specific methods varied, the present study broadly demonstrates the importance of controlling and documenting standardisation procedures prior to body composition assessments across distinct assessment technologies, particularly for longitudinal investigations. Additionally, there are meaningful differences in the ability of common methods to track longitudinal body composition changes.