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Herein, we determined if a multi-ingredient supplement (NAD3; 312 mg of combined Wasabia japonica extract, theacrine, and copper (I)niacin chelate) versus a placebo (CTL) affected peripheral blood mononuclear (PMBC) transcriptomic, DNA methylation, and sirtuin activity profiles in middle-aged adults after 12 weeks of supplementation. Several mRNAs demonstrated interactions (n = 148 at ±1.5-fold change, p < 0.01), and more stringent filtering indicated that 25 mRNAs were upregulated and 29 were downregulated in the NAD3 versus CTL group. Bioinformatics on these 64 mRNAs suggested that DNA conformational alterations may have been promoted with NAD3 supplementation, and this was corroborated with more CpG sites being hypermethylated (p < 0.001) in the CTL versus the NAD3 group when examining pre- to post-intervention changes (369 versus 35). PBMC SIRT activity decreased in CTL participants (p < 0.001), but not in NAD3 participants (p = 0.289), and values at 12 weeks trended higher in NAD3 participants (p = 0.057). Interestingly, the pre- to post- changes in SIRT activity values significantly correlated with changes in PBMC NAD+: NADH values obtained from a previous investigation in these participants (r = 0.534, p = 0.015). In conclusion, the current mRNA and DNA methylation data indirectly suggest that NAD3 supplementation may affect PBMC DNA conformation, while other direct assays suggest that NAD3 supplementation maintains SIRT activity through the potential maintenance of NAD+: NADH levels. However, these results are preliminary due to limited n-sizes and the study being performed in middle-aged adults. [ABSTRACT FROM AUTHOR]

It is universally accepted that resistance training promotes increases in muscle strength and hypertrophy in younger and older populations. Although less investigated, studies largely suggest resistance training results in lower skeletal muscle mitochondrial volume; a phenomenon which has been described as a "dilution of the mitochondrial volume" via resistance training. While this phenomenon is poorly understood, it is likely a result of muscle fiber hypertrophy outpacing mitochondrial biogenesis. Critically, there is no evidence to suggest resistance training promotes a net loss in mitochondria. Further, given the numerous reports suggesting resistance training does not decrease and may even increase VO2 max in previously untrained individuals, it is plausible certain aspects of mitochondrial function may be enhanced with resistance training, and this area warrants further research consideration. Finally, there are emerging data suggesting resistance training may affect mitochondrial dynamics. The current review will provide an in-depth discussion of these topics and posit future research directions which can further our understanding of how resistance training may affect skeletal muscle mitochondrial physiology. [ABSTRACT FROM AUTHOR]

Female athletes are at an elevated risk for tearing their anterior cruciate ligament, compared to their male counterparts. Though injury screening clinical tests and neuromuscular training programs have been widely implemented, injury rates remain high among female athletes. The purpose of this study was to examine the relationship between serum relaxin concentrations and knee valgus during three clinical tests (single leg squat, drop vertical jump, and single leg crossover dropdown). Twenty-two female athletes volunteered. Participants were scheduled for collection during the mid-luteal phase, when serum relaxin concentrations are known to be measurable. Blood samples were collected, and serum relaxin concentrations were quantified. Kinematic data were collected while participants performed the three clinical tests. Regression analyses revealed statistically significant relationships between serum relaxin concentrations and knee valgus throughout all tests. These findings suggest that serum relaxin concentrations and knee valgus are not independent of each other and more holistic approaches may be necessary to truly map out the risk for injury and ultimately reduce the rate of anterior cruciate ligament injuries. Thus, concluding that knee valgus, a highly utilized modifiable biomechanical risk factor, and relaxin, a hormone that has been associated with anterior cruciate ligament injury in female athletes, are related to each other. [ABSTRACT FROM AUTHOR]

We examined molecular mechanisms that were altered during rapid soleus (type I fiber-dominant) and plantaris (type II fiber-dominant) hypertrophy in rats. Twelve Wistar rats (3.5 mo old; 6 female, 6 male) were subjected to surgical right-leg soleus and plantaris dual overload [synergist ablation (SA)], and sham surgeries were performed on left legs (CTL). At 14 days after surgery, the muscles were dissected. Plantaris mass was 27% greater in the SA than CTL leg (P < 0.001), soleus mass was 13% greater in the SA than CTL leg (P < 0.001), and plantaris mass was higher than soleus mass in the SA leg (P = 0.001). Plantaris total RNA concentrations and estimated total RNA levels (suggestive of ribosome density) were 19% and 47% greater in the SA than CTL leg (P < 0.05), protein synthesis levels were 64% greater in the SA than CTL leg (P = 0.038), and satellite cell number per fiber was 60% greater in the SA than CTL leg (P = 0.003); no differences in these metrics were observed between soleus SA and CTL legs. Plantaris, as well as soleus, 20S proteasome activity was lower in the SA than CTL leg (P < 0.05), although the degree of downregulation was greater in the plantaris than soleus muscle (−63% vs. −20%, P = 0.001). These data suggest that early-phase plantaris hypertrophy occurs more rapidly than soleus hypertrophy, which coincided with greater increases in ribosome biogenesis, protein synthesis, and satellite cell density, as well as greater decrements in 20S proteasome activity, in the plantaris muscle. [ABSTRACT FROM AUTHOR]

Background: This investigation examined the safety and efficacy of a silica-based mineral antioxidant complex (MAC) that has been suggested to influence body water and buffer lactate. Methods: In a double-blind, randomized crossover design, male participants completed testing for 3 conditions: water only (baseline), rice flour (placebo), and MAC supplementation. Participants visited the laboratory on 5 occasions: familiarization, baseline, Testing Day 1, washout, and Testing Day 2. Baseline and Testing Days 1 and 2 consisted of fasting blood, pre- to postexercise body-water assessment and determination of VO2peak on a cycle ergometer. The supplementation protocols were separated by 1 wk and balanced to minimize an order effect. Results: No differences between conditions were found for heart rate, blood pressure, or serum-safety markers (p > .05). Before exercise there were no differences between conditions for total body water (TBW), intracellular water (ICW), or extracellular water (ECW). No significant interactive effects for supplementation and exercise were found for TBW, ICW, or ECW (p > .05). A time effect for TBW (p < .01) and ICW (p < .001) was present. Within-group changes in TBW occurred in the MAC condition, and within-group changes for ICW occurred in the MAC and placebo conditions. Ratings of perceived exertion and blood lactate increased (p < .05) with exercise. No significant effects were found for performance variables. Conclusions: MAC supplementation had no impact on aerobic exercise performance and lactate response. Increases in TBW and ICW occurred after MAC consumption, but these changes appeared to have minimal physiological impact. [ABSTRACT FROM AUTHOR]

Purpose: We sought to compare the effects of external pneumatic compression (EPC) and sham when used concurrently with resistance training on performance-related outcomes and molecular measures related to recovery. Methods: Twenty (N = 20) resistance-trained male participants (aged 21.6±2.4 years) were randomized to balanced sham or EPC intervention groups. The protocol consisted of 3 consecutive days of heavy, voluminous back squat exercise followed by EPC/sham treatment (Days2-4) and 3 consecutive days of recovery (Days5-7) with EPC/sham only on Days5-6. On Day1 (PRE), and Days3-7, venipuncture, flexibility and pressure-to-pain threshold (PPT) measures were performed. Vastsus lateralis muscle tissue was biopsied at PRE, 1-h post-EPC/sham treatment on Day2 (POST1) and 24-h post-EPC/sham treatment on Day7 (POST2). Isokinetic peak torque was assessed at PRE and POST2. Results: Peak isokinetic strength did not change from PRE to POST2 in either group. The PPT was significantly lower on Days3-6 with sham, indicating greater muscle soreness, though this was largely abolished in the EPC group. A significant decrease in flexibility with sham was observed on Day3 (+16.2±4.6% knee joint angle; P<0.01) whereas there was no change with EPC (+2.8±3.8%; P>0.01). Vastus lateralis poly-ubiquitinated proteins significantly increased at the POST2 time point relative to PRE with sham (+66.6±24.6%; P<0.025) and were significantly greater (P<0.025) than those observed with EPC at the same time point (-18.6±8.5%). 4-hydroxynonenal values were significantly lower at POST2 relative to PRE with EPC (-16.2±5.6%; P<0.025) and were significantly lower (P<0.025) than those observed with sham at the same time point (+11.8±5.9%). Conclusion: EPC mitigated a reduction in flexibility and PPT that occurred with sham. Moreover, EPC reduced select skeletal muscle oxidative stress and proteolysis markers during recovery from heavy resistance exercise. [ABSTRACT FROM AUTHOR]

Key points Selective breeding experiments with laboratory rodents have demonstrated the heritability of voluntary exercise., We performed RNA sequencing and bioinformatics analyses of the reward and pleasure hub in the brain - the nucleus accumbens - in rats selectively bred for low voluntary running (LVR) versus high voluntary running (HVR)., The discovery of unique genes and 'cell cycle'-related gene pathways between lines guided our hypothesis that neuron maturation may be lower in LVR rats., Testing of this hypothesis revealed that the LVR line inherently possessed fewer mature medium spiny neurons and fewer immature neurons than their HVR counterparts. However, minimal running in LVR rats appeared to rescue and/or reverse these effects., Neuron maturation in the nucleus accumbens is related to low running voluntary behaviour in our model; this allows researchers to understand the potential neural mechanisms that underlie the motivations for low physical activity behaviour., Abstract We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVRnon-run and HVRnon-run), as well as in rats after 6 days of voluntary wheel running (LVRrun and HVRrun). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that 'cell cycle'-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9-10 LVRnon-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons ( P < 0.001) and fewer immature (Dcx-positive) neurons ( P < 0.001) than their G9-10 HVR counterparts. However, voluntary running wheel access in our G9-10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. [ABSTRACT FROM AUTHOR]

To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P < 0.05) compared with lean pigs. RNA-seq revealed a 37% increase in the total transcript number in the OMAT of obese pigs. Ingenuity Pathway Analysis showed transcripts in obese OMAT were primarily enriched in the following categories: 1) development, 2) cellular function and maintenance, and 3) connective tissue development and function, while transcripts associated with RNA posttranslational modification, lipid metabolism, and small molecule biochemistry were reduced. DAVID and Gene Ontology analyses showed that many of the classically recognized gene pathways associated with adipose tissue dysfunction in obese adults including hypoxia, inflammation, angiogenesis were not altered in OMAT in our model. The current study indicates that obesity in juvenile Ossabaw swine is characterized by increases in overall OMAT transcript number and provides novel data describing early transcriptomic alterations that occur in response to excess caloric intake in visceral adipose tissue in a pig model of childhood obesity. [ABSTRACT FROM AUTHOR]

We examined how gavage feeding extensively hydrolyzed whey protein (WPH) versus a native whey protein concentrate (WPC) transiently affected serum biochemical profiles in rodents. Male Wistar rats (250-300 g) were 8 h fasted and subsequently fed isonitrogenous amounts of WPH or WPC, or remained unfed (control). Animals were sacrificed 15 min, 30 min, and 60 min post-gavage for serum extraction, and serum was analyzed using untargeted global metabolic profiling via gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS platforms. We detected 333 serum metabolites amongst the experimental and control groups. Both WPH and WPC generally increased amino acids (1.2-2.8-fold), branched-chain amino acids (1.2-1.7-fold), and serum di- and oligo-peptides (1.1-2.7-fold) over the 60 min time course compared with control ( q < 0.05). However, WPH increased lysine (false discovery rate using a q-value <0.05) and tended to increase isoleucine and valine 15 min post-feeding ( q < 0.10) as well as aspartylleucine 30 min post-feeding compared with WPC ( q < 0.05). While both protein sources led to a dramatic increase in free fatty acids compared with control (up to 6-fold increases, q < 0.05), WPH also uniquely resulted in a 30 min post-feeding elevation in free fatty acids compared with WPC ( q < 0.05), an effect which may be due to the robust 30 min postprandial increase in epinephrine in the WPH cohort. These data provide a unique postprandial time-course perspective on how WPH versus WPC feedings affect circulating biochemicals and will guide future research comparing these 2 protein sources. [ABSTRACT FROM AUTHOR]

The cessation of physical activity in rodents and humans initiates obesogenic mechanisms. The overall purpose of the current study was to determine how the cessation of daily physical activity in rats at 49-56 days of age and at 70-77 days of age via wheel lock (WL) affects adipose tissue characteristics. Male Wistar rats began voluntary running at 28 days old and were either killed at 49-56 days old or at 70-77 days old. Two cohorts of rats always had wheel access (RUN), a second two cohorts of rats had wheel access restricted during the last 7 days (7d-WL), and a third two cohorts of rats did not have access to a voluntary running wheel after the first 6 days of (SED). We observed more robust changes with WL in the 70- to 77-day-old rats. Compared with RUN rats, 7d-WL rats exhibited greater rates of gain in fat mass and percent body fat, increased adipocyte number, higher percentage of small adipocytes, and greater cyclin A1 mRNA in epididymal and perirenal adipose tissue. In contrast, 49- to 56-day-old rats had no change in most of the same characteristics. There was no increase in inflammatory mRNA expression in either cohort with WL. These findings suggest that adipose tissue in 70- to 77-day-old rats is more protected from WL than 49- to 56-day-old rats and responds by expansion via hyperplasia. [ABSTRACT FROM AUTHOR]

Purpose: The impact of prophylactic supplementation of N-acetyl-cysteine (NAC) and epigallocatechin gallate (EGCG) on intramuscular expression of proteolytic genes after unaccustomed eccentric muscle contractions was investigated. Methods: Thirty apparently healthy males (mean±SD: 20.0±1.8years, 175±7.1cm, 76.1±16.9kg) ingested daily either 1800mg of NAC or 1800mg of EGCG (98% total polyphenols, 80% total catechins, and 50% EGCG), or 1000mg of a glucomannan placebo (PLA) in a double blind, prophylactic fashion for 14days. Subjects then completed an unaccustomed eccentric exercise bout (100 repetitions at 30°s−1) using the dominant knee extensors. Skeletal muscle biopsies were collected from the vastus lateralis at baseline and both 6 and 24h after exercise. The expression of proteolytic genes [i.e., muscle ring-finger 1 (MuRF1), atrogin-1, α-type 20S subunit C2 (HC2), α-type 20S subunit C3 (HC3), ubiquitin protein ligase 3B (UBE3B), μ-calpain, and m-calpain] was quantified using real-time RT-PCR. Separate 3×3 (group×time) repeated measures ANOVAs were used to analyze changes in gene expression over time between groups. Results: No significant group×time interactions were detected between groups for the expression of any of the atrogenes or calpains (p >0.05). Significant main effects for time identified increases in MuRF1 (6h: 5.3±10.8 fold; p =0.046), UBE3B (6h: 5.3±7.7 fold; p =0.006; 24h: 3.3±4.5 fold; p =0.005), and m-calpain expression (6h: 2.7±4.4 fold; p =0.045) in all participants following exercise. Increases approached significance in HC2 (6h: 1.9±2.4 fold; p =0.079; 24h: 1.6±1.9 fold; p =0.084) and m-calpain expression (24h: 1.8±2.3 fold; p =0.084) following exercise. Conclusions: Prophylactic supplementation of NAC and EGCG did not impact acute changes in skeletal muscle proteolytic gene expression following eccentric exercise. Eccentric muscle contractions elevated MuRF1 and UBE3B, while m-calpain and HC2 mRNA tended to increase. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to partially phenotype male and female rats from generations 8-10 (G8-G10) that had been selectively bred to possess low (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with wheels, 34-day-old G8 male and female LVRs ran shorter distances (P < 0.001), spent less time running (P < 0.001), and ran slower (P < 0.001) than their G8 male and female HVR counterparts, respectively. HVR and LVR lines consumed similar amounts of standard chow with or without wheels. No inherent difference existed in PGC-1α mRNA in the plantaris and soleus muscles of LVR and HVR nonrunners, although G8 LVR rats inherently possessed less NADH-positive superficial plantaris fibers compared with G8 HVR rats. While day 28 body mass tended to be greater in both sexes of G9-G10 LVR nonrunners vs. G9-G10 HVR nonrunners (P > 0.06), body fat percentage was similar between lines. G9-G10 HVRs had fat mass loss after 6 days of running compared with their prerunning values, while LVR did not lose or gain fat mass during the 6-day voluntary running period. RNA deep sequencing efforts in the nucleus accumbens showed only eight transcripts to be > 1.5-fold differentially expressed between lines in HVR and LVR nonrunners. Interestingly, HVRs presented less Oprd1 mRNA, which ties in to potential differences in dopaminergic signaling between lines. This unique animal model provides further evidence as to how exercise may be mechanistically regulated. [ABSTRACT FROM AUTHOR]

The article discusses research investigating the effects of aging and sequential resistance exercise on housekeeping gene (HKG) messenger RNA (mRNA) expression in human skeletal muscle. The team recruited 10 college-aged men between 18-25 years and 10 older men between 60-76 years and had them perform three lower-body resistance exercise bouts. Muscle samples were obtained after each bout and analyzed via real-time reverse transcription-polymerase chain reaction (RT-PCR) methods.

The article outlines the protocol used when performing the electrophoretic separation of myosin heavy chain isoforms using a modified mini gel system and discusses potential troubleshooting considerations for researchers performing this intricate methodology. A need for modifying protocols which will be seen as a result of additional technologies which will become available is discussed.

According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2-19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults. Examining the effects of inactivity on physiological homeostasis during youth is crucial given that 58% of children between the ages 6-11 yr old fail to obtain the recommended 60 min/day of physical activity and 92% of adolescents fail to achieve this goal [Troiano et al. Med Sci Sports Exerc. 40, 2008]. Nonetheless, invasive mechanistic studies in children linking diminished physical activity with metabolic maladies are lacking for obvious ethical reasons. The rodent wheel lock (WL) model was adopted by our laboratory and others to study how different organ systems of juvenile rats respond to a cessation of daily physical activity. Our WL model houses rats in cages equipped with voluntary running wheels starting at 28 days of age. After a certain period of voluntary running (3 to 6 wk), the wheels are locked, thus preventing the rats' primary source of physical activity. The studies discussed herein suggest that obesity-associated maladies including skeletal muscle insulin resistance, hypothalamic leptin resistance, fatty acid oxidation impairments in skeletal muscle and adipose tissue, nonalcoholic fatty liver disease, and endothelial dysfunction are initiated in juvenile animals that are restrained from voluntary exercise via WL. The use of the juvenile rodent WL or other inactivity models will continue to provide a powerful clinical translational tool that can be used for primordial prevention of human childhood obesity. [ABSTRACT FROM AUTHOR]

Abstract: Dopamine signaling in the nucleus accumbens (NAc) has been postulated to influence reward development towards drugs of abuse and exercise. Herein, we used generation 4–5 rats that were selectively bred to voluntary run high (HVR) versus low (LVR) distances in order to examine if dopamine-like 1 (D1) receptor modulation in the NAc differentially affects nightly voluntary wheel running between these lines. A subset of generation 5–6 HVR and LVR rats were also used to study the mRNA expression of key genes related to reward and addiction in the NAc (i.e., DRD1, DRD5, DRD2, Nr4a2, FosB, and BDNF). In a crossover fashion, a D1-like agonist SKF 82958 (2μg per side) or D1-like full antagonist SCH 23390 (4μg per side) was bilaterally injected into the NAc of HVR and LVR female Wistar rats prior to their high running nights. Notably, during hours 2–4 (between 2000 and 2300) of the dark cycle there was a significant decrement in running distances in the HVR rats treated with the D1 agonist (p=0.025) and antagonist (p=0.017) whereas the running distances in LVR rats were not affected. Interestingly, HVR and LVR rats possessed similar NAc concentrations of the studied mRNAs. These data suggest that: a) animals predisposed to run high distances on a nightly basis may quickly develop a rewarding response to exercise due to an optimal D1-like receptor signaling pathway in the NAc that can be perturbed by either activation or blocking, b) D1-like agonist or antagonist injections do not increase running distances in rats that are bred to run low nightly distances, and c) running differences between HVR and LVR animals are seemingly not due to the expression of the studied mRNAs. Given the societal prevalence of obesity and extraneous physical inactivity, future studies should be performed in order to further determine the culprit for the low running phenotype observed in LVR animals. [Copyright &y& Elsevier]

Abstract: The purpose of this review is to examine the literature in an attempt to elucidate a biomechanical basis for glaucomatous cupping. In particular, this work focuses on the role of biomechanics in driving connective tissue remodeling in the progression of laminar morphology from a normal state to that of an excavated glaucomatous state. While there are multiple contributing factors to the pathogenesis of glaucoma, we focus on laminar extracellular matrix (ECM) remodeling in glaucoma and the feedback mechanisms and signals that may guide progressive laminar cupping. We review the literature on the potential mechanisms of glaucomatous changes in the laminar ECM at the anatomic, structural, cellular and subcellular levels in the context of the biomechanical paradigm of glaucomatous onset and progression. Several conclusions can be drawn from this review. First, extensive remodeling of the lamina cribrosa ECM occurs in primary open angle glaucoma. Second, there is surprisingly little evidence to support acute mechanical damage to the lamina as the principal mechanism of cupping. Third, ONH astrocytes and lamina cribrosa cells can sense their mechanical environment and respond to mechanical stimuli by remodeling the ECM. Fourth, there is evidence suggesting that chronic remodeling of the lamina results in a progressive posterior migration of the laminar insertion into the canal wall, which eventually results in the posterior lamina inserting into the pia mater. Finally, modeling studies suggest that laminar remodeling may be a biomechanical feedback mechanism through which cells modify their environment in an attempt to return to a homeostatic mechanical environment. It is plausible that biomechanics-driven connective tissue remodeling is a mechanism in the progression of laminar morphology from a normal state to that of a cupped, excavated glaucomatous state. [Copyright &y& Elsevier]

To determine the influence of age and resistance exercise on myostatin pathway–related genes, younger (n = 10; 28 ± 5 years) and older (n = 10; 68 ± 6 years) men underwent four testing conditions (T1–T4). A baseline (T1) muscle sample was obtained, whereas the second and third biopsies were obtained 48 hours following the first and second training sessions (T2, T3), and a final biopsy was taken 24 hours following T3. The training sessions consisted of 3 sets of 10 repetitions (80% of one repetition maximum) on leg press, hack squat, and leg extension exercises. Follistatin (FST) messenger RNA was greater in older compared with younger men at T1 and T2 (p < .05). Follistatin-like 3 (FSTL3) messenger RNA was greater in older compared with younger men at T1 and T4 (p < .05). In older men, there was a significant decrease in myostatin (MSTN) messenger RNA at T4 (p < .05). Older men contained less active (Ser-425 phosphorylated) SMAD3 (p-SMAD3) protein than younger men at T3 and T4 (p < .05).Although it is well known that younger individuals possess a greater hypertrophic potential to resistance exercise, it appears that older individuals may paradoxically possess a more favorable resistance exercise response regarding myostatin pathway–related genes and a protein marker of pathway activity. Future research is warranted to examine the physiological significance of this age-dependent mechanism. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: We examined whether the ingestion of a hydrothermally modified starch (HMS) would alter metabolic and hormonal responses to prolonged cycling compared with maltodextrin (MAL). Methods: Nine male cyclists (30 ± 2 y, 79.2 ± 2.1 kg, 4.7 ± 0.1 L of O2/min, 7.5 ± 1.3 y training) fasted 10 h before cycling for 150 min at 70% peak oxygen consumption and completing a cycling-to-exhaustion trial at 100% peak oxygen consumption. Participants ingested 1g/kg of HMS or MAL 30 min before and within 10 min of completing the bout. Blood samples were provided every 15 min before, during, and 90 min after exercise. Expired gases were collected every 30 min during exercise. In a crossover, randomized, and double-blind fashion, identical testing was completed 1 wk later. Results: Primary findings from this study were that 1) increases in serum glucose were greater during MAL (peak 9.5 mM) versus HMS (peak 7.4 mM, P ≤ 0.01), 2) insulin levels were significantly lower during HMS (peak 2.5 μIU/mL) versus MAL (peak 20.3 μIU/mL, P < 0.001), and 3) HMS was associated with greater fat breakdown as indicated by the increased serum non-esterified fatty acids (P < 0.01) and glycerol levels (P < 0.05). Conclusion: Ingestion of a low-glycemic HMS before prolonged cycling exercise blunted the initial spike in serum glucose and insulin and increased the breakdown in fat compared with MAL. [Copyright &y& Elsevier]

This study examined how multiple bouts of conventional resistance training affected the mRNA expression of transcripts and a protein associated with satellite cell activity in human skeletal muscle. Ten younger men (means ± SE; age, 21.0 ± 0.5 years; body mass, 82.3 ± 4.2 kg; height, 178.4 ± 2.2 cm; percent body fat, 15.4% ± 2.9%) and 10 older men (age, 66.4 ± 1.6 years; body mass, 94.2 ± 3.7 kg; height, 180.9 ± 2.2 cm; percent body fat, 27.4% ± 1.8%) completed 3 lower-body workouts (Monday, Wednesday, Friday; 9 sets of 10 repetitions at 80% 1 repetition maximum). Vastus lateralis muscle biopsies were collected prior to intervention (T1), 48 h following workout 1 (T2), 48 h following workout 2 (T3), and 24 h following workout 3 (T4). Real-time reverse transcription-polymerase chain reaction was performed to assess genes of interest, and muscle proliferating cell nuclear antigen (PCNA) was assessed using Western blotting. The CYCLIN D1 gene was expressed more highly in the older vs. younger men (p < 0.05), whereas the expression of all other genes and muscle PCNA were similar between age groups. MYOD mRNA expression increased at T2 (p < 0.05) and MHCEMB gene expression modestly increased (p < 0.05) at T4 relative to baseline expression values in the younger men. Baseline elevations in CYCLIN D1 mRNA expression in older persons may indicate that a compensatory expression of this transcript is occurring in an attempt to retain the muscle's proliferative potential. Increases in MYOD and MHCEMB indicate that 1 week of conventional resistance exercise may i crease myogenic activity, including satellite cell proliferation and differentiation, respectively, in younger men. [ABSTRACT FROM AUTHOR]

The article presents the results of a study which investigated the relationship between aging, gene expression of androgen and megalin receptors in muscle, exercise and sarcopenia. An overview of related previous research is provided, along with details of the experimental protocol, which involved muscle biopsies.

The article presents the results of a study which investigated the use of a thermogenic weight loss supplement, as part of a body composition modification program which also included a meal replacement and exercise. An overview of related previous research is provided, along with details of the experimental protocol, which was double-blind and placebo-controlled .

The article presents the results of a study which investigated the impact of age on the hormonal effects of resistance training, focusing on concentrations of hormones such as cortisol, and proteolytic signaling. An overview of related previous research is provided, along with details of the experimental protocol, which involved leg exercises and muscle biopsies.

Genes and proteins involved in insulin-like growth factor (IGF)-1 signaling are thought to be differentially expressed in older versus younger mammalian skeletal muscle following acute exercise. The purpose of this study was to examine how multiple bouts of conventional resistance training meant to elicit hypertrophy affect the mRNA expression of IGF-1EA and IGF-1EC (MGF) as well as the expression of total IGF-1 peptides in human skeletal muscle. Ten younger (18-25 years) and 10 older (60-75 years) males completed three sequential workouts (M, W, F) consisting of nine sets of lower body exercises with ten repetitions per set at an intensity of 80% of one repetition maximum. Vastus lateralis muscle biopsies were collected prior to intervention (T1), 48 h following workout 1 (T2), 48 h following workout 2 (T3), and 24 h following workout 3 (T4). RT-PCR was performed to assess baseline and changes in MGF and IGF-IEA mRNA. Samples were also assayed for total muscle IGF-1 peptides using ELISA-based methods. There were no baseline differences in MGF or IGF-1EA mRNA expression and IGF-1 peptides between age groups. Interestingly, MGF expression increased at T2-T4 in the older group relative to baseline values (p < 0.05), albeit muscle IGF-1EA mRNA and IGF-1 peptides remained stably expressed throughout the intervention in both age groups. Repeated conventional exercise bouts resulted in a summative increase in MGF mRNA expression only in older individuals which is contrary to previous research examining this gene at different post-exercise time points, albeit the physiological consequences of these findings remain unknown. [ABSTRACT FROM AUTHOR]

The article presents a study on the effects of consuming carbohydrate or protein versus a noncaloric placebo in the myogenic expression of cell activation after exercise. Methods were executed by 10 men in three resistance exercises including bilateral hack squat, leg extension and leg press. The researchers also used the absorption of carbohydrates, protein or placebo 30 minutes before workout. Preceding analysis of the study includes the RNA analysis, performing real time- polymerase chain reaction (PCR) and muscle DNA determination. Moreover, nonparametric statistics analysis such as the Mann- Whitney U statistics and Friedman test reasons that the tandem of cell cycle regulator gene and DNA proved that satellite cell activation occur at early after exercise.

The article reports on research conducted on the effect gender had on the metabolic impact of a thermogenic energy drink which contained caffeine, epigallocatechin gallate and taurine. Researchers evaluated 30 men and 30 women who ingested 336 milliliters of the thermogenic drink or a placebo and measured levels of glycerol and fatty acids in their blood. They found that women had increases in fatty acids and men had increases in glycerol and that men lost more body fat due to the drink.

The article presents the results of a study which investigated the ratios of RNA, DNA, and protein in the muscles of younger and older men, and the impact of weight training on these ratios. An overview of related previous research is provided, along with details of the experimental protocol. It was found that the muscles of older men were less efficient at muscle protein synthesis.

The article reports on the results of research which was conducted to determine the expression of androgen-regulated genes before and after a resistance exercise session in younger and older men. Researchers found that free testosterone levels were greater in younger men at all times, that preexercise human growth hormone levels between age groups were similar and that human growth hormone increased immediately post exercise in both groups with a greater response occurring in the younger men.

Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization‐induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty‐nine healthy, college‐aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652. What is the central question of this study?Action observation and mental imagery (AOMI) may be a possible and potentially promising rehabilitation strategy via facilitation of neural adaptations, whereas neuromuscular electrical stimulation (NMES) may augment muscle strength and mass via peripheral mechanisms. We compared the ability of these interventions to distinctly preserve strength versus mass during one week of knee joint immobilization.What is the main finding and its importance?Effect sizes suggested that AOMI preserved voluntary strength, and may be used therapeutically to target neural adaptations during immobilization. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the effects of progressive overload in resistance training on muscle strength and cross-sectional area (CSA) by specifically comparing the impact of increasing load (LOADprog) versus an increase in repetitions (REPSprog). We used a within-subject experimental design in which 39 previously untrained young persons (20 men and 19 women) had their legs randomized to LOADprog and REPSprog. Outcomes were assessed before and after 10 weeks of training. Muscle strength was assessed using the one repetition maximum (1RM) test on the leg extension exercise, and the CSA of the vastus lateralis was assessed by ultrasonography. Both protocols increased 1RM values from pre (LOADprog: 52.90±16.32 kg; REPSprog: 51.67±15.84 kg) to post (LOADprog: 69.05±18.55 kg, REPSprog: 66.82±17.95 kg), with no difference between them (P +>+0.05). Similarly, both protocols also increased in CSA values from pre (LOADprog: 21.34±4.71 cm²; REPSprog: 21.08±4.62 cm²) to post (LOADprog: 23.53±5.41 cm², REPSprog: 23.39±5.19 cm²), with no difference between them (P +>+0.05). In conclusion, our findings indicate that the progression of overload through load or repetitions can be used to promote gains in strength and muscle hypertrophy in young men and women in the early stages of training. [ABSTRACT FROM AUTHOR]

To investigate the gut-brain axis, we explored the relationships among mood disturbance (MD), diet quality (DQ), and fecal microbiota in free-living adults. A cross-sectional analysis was conducted with data from 75 healthy adults enrolled in two studies. Anthropometrics, 16s rRNA gene sequencing of fecal microbes, DQ as assessed by Healthy Eating Index-2015 (HEI), and MD determined by Profile of Mood States (POMS) were included. Alpha-diversity and DQ differences were explored between low (n = 37) and high MD (n = 38) groups. Spearman correlations were used to investigate relationships between alpha-diversity, DQ, and POMS subscales. Moderation analysis explored the effect of HEI score on the relationship between MD and alpha-diversity. Participants were mostly white (67%), 54.5 years old (±11.8), and overweight (28.5 ± 6.5 kg/m2). Shannon and Simpson indices indicate higher alpha-diversity in participants with low MD compared to high MD (p = 0.004 and p = 0.008, respectively). Simpson and Shannon indices were correlated with subscale of anger (rho = −0.303, p = 0.011; rho = −0.265, p = 0.027, respectively)and total MD (rho = −0.404, p = 0.001; rho = −0.357, p = 0.002, respectively). Refined grains were associated with fatigue and tension subscales (rho = 0.428, p < 0.001; rho = 0.302, p = 0.014, respectively). DQ did not significantly moderate the relationship between alpha-diversity and mood disturbance (F(7, 53) = 2.00, p = 0.072, R2 = 0.209). Shannon index was a significant predictor of MD (b = −4.39, t(53) = −2.55, p = 0.014), but total HEI score and the interaction (Shannon index*HEI score) were not significant. Greater bacterial diversity was associated with lower MD, and DQ was associated with various mood state subscales in this sample of adults. [ABSTRACT FROM AUTHOR]

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training (2 days/week for 8 weeks) on denervated myofibers, senescent cells, and associated protein markers in apparently healthy middle-aged participants (MA, 55 ± 8 years old, 17 females, 9 males). We obtained dual-leg vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training. Fiber cross-sectional area (fCSA), satellite cells (Pax7+), denervated myofibers (NCAM+), senescent cells (p16+ or p21+), proteins associated with denervation and senescence, and senescence-associated secretory phenotype (SASP) proteins were analyzed from biopsy specimens. Leg extensor peak torque increased after training (p < .001), while VL mCSA trended upward (interaction p = .082). No significant changes were observed for Type I/II fCSAs, NCAM+ myofibers, or senescent (p16+ or p21+) cells, albeit satellite cells increased after training (p = .037). While >90% satellite cells were not p16+ or p21+, most p16+ and p21+ cells were Pax7+ (>90% on average). Training altered 13 out of 46 proteins related to muscle-nerve communication (all upregulated, p < .05) and 10 out of 19 proteins related to cellular senescence (9 upregulated, p < .05). Only 1 out of 17 SASP protein increased with training (IGFBP-3, p = .031). In conclusion, resistance training upregulates proteins associated with muscle-nerve communication in MA participants but does not alter NCAM+ myofibers. Moreover, while training increased senescence-related proteins, this coincided with an increase in satellite cells but not alterations in senescent cell content or SASP proteins. These latter findings suggest shorter term resistance training is an unlikely inducer of cellular senescence in apparently healthy middle-aged participants. However, similar study designs are needed in older and diseased populations before definitive conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Peripheral quantitative computed tomography (pQCT) has recently expanded to quantifying skeletal muscle, however its validity to determine muscle cross‐sectional area (mCSA) compared to magnetic resonance imaging (MRI) is unknown. Eleven male participants (age: 22 ± 3 y) underwent pQCT and MRI dual‐leg mid‐thigh imaging before (PRE) and after (POST) 6 weeks of resistance training for quantification of mid‐thigh mCSA and change in mCSA. mCSA agreement at both time points and absolute change in mCSA across time was assessed using Bland‐Altman plots for mean bias and 95% limits of agreement (LOA), as well as Lin's concordance correlation coefficients (CCC). Both pQCT and MRI mCSA increased following 6 weeks of resistance training (∆mCSApQCT: 6.7 ± 5.4 cm2, p < 0.001; ∆mCSAMRI: 6.0 ± 6.4 cm2, p < 0.001). Importantly, the change in mCSA was not different between methods (p = 0.39). Bland‐Altman analysis revealed a small mean bias (1.10 cm2, LOA: −6.09, 8.29 cm2) where pQCT tended to overestimate mCSA relative to MRI when comparing images at a single time point. Concordance between pQCT and MRI mCSA at PRE and POST was excellent yielding a CCC of 0.982. For detecting changes in mCSA, Bland‐Altman analysis revealed excellent agreement between pQCT and MRI (mean bias: −0.73 cm2, LOA: −8.37, 6.91 cm2). Finally, there was excellent concordance between pQCT and MRI mCSA change scores (CCC = 0.779). Relative to MRI, pQCT imaging is a valid technique for measuring both mid‐thigh mCSA at a single time point and mCSA changes following a resistance training intervention. [ABSTRACT FROM AUTHOR]

An increase in mechanical loading, such as that which occurs during resistance exercise, induces radial growth of muscle fibers (i.e. an increase in cross-sectional area). Muscle fibers are largely composed of myofibrils, but whether radial growth is mediated by an increase in the size of the myofibrils (i.e. myofibril hypertrophy) and/or the number of myofibrils (i.e. myofibrillogenesis) is not known. Electron microscopy (EM) can provide images with the level of resolution that is needed to address this question, but the acquisition and subsequent analysis of EM images is a time- and cost-intensive process. To overcome this, we developed a novel method for visualizing myofibrils with a standard fluorescence microscope (fluorescence imaging of myofibrils with image deconvolution [FIM-ID]). Images from FIM-ID have a high degree of resolution and contrast, and these properties enabled us to develop pipelines for automated measurements of myofibril size and number. After extensively validating the automated measurements, we used both mouse and human models of increased mechanical loading to discover that the radial growth of muscle fibers is largely mediated by myofibrillogenesis. Collectively, the outcomes of this study offer insight into a fundamentally important topic in the field of muscle growth and provide future investigators with a time- and cost-effective means to study it. [ABSTRACT FROM AUTHOR]

This study investigated the impact of an isocaloric and isonitrogenous ketogenic diet (KD) versus a traditional western diet (WD) on changes in body composition, performance, blood lipids, and hormonal profiles in resistance-trained athletes. Twenty-five college-aged men were divided into a KD or traditional WD from weeks 1 to 10, with a reintroduction of carbohydrates from weeks 10 to 11, while participating in a resistance training program. Body composition, strength, power, and blood lipid profiles were determined at weeks 0, 10, and 11. A comprehensive metabolic panel and testosterone levels were also measured at weeks 0 and 11. Lean body mass (LBM) increased in both the KD and WD groups (2.4% and 4.4%, p < 0.01) at week 10. However, only the KD group showed an increase in LBM between weeks 10 and 11 (4.8%, p < 0.0001). Finally, fat mass decreased in both the KD (-2.2 ± 1.2 kg) and WD groups (-1.5 ± 1.6 kg). Strength and power increased to the same extent in the WD and KD conditions from weeks 1 to 11. No changes in any serum lipid measures occurred from weeks 1 to 10; however, a rapid reintroduction of carbohydrate from weeks 10 to 11 raised plasma triglyceride levels in the KD group. Total testosterone increased significantly from weeks 0 to 11 in the KD diet (118 ng·dl-1) as compared to the WD (-36 ng·dl-1) from pre to post while insulin did not change. The KD can be used in combination with resistance training to cause favorable changes in body composition, performance, and hormonal profiles in resistance-trained men. [ABSTRACT FROM AUTHOR]

We recently reported that vastus lateralis (VL) cross‐sectional area (CSA) increases after 7 weeks of resistance training (RT, 2 days/week), with declines occurring following 7 weeks of subsequent treadmill high‐intensity interval training (HIIT) (3 days/week). Herein, we examined the effects of this training paradigm on skeletal muscle proteolytic markers. VL biopsies were obtained from 11 untrained college‐aged males at baseline (PRE), after 7 weeks of RT (MID), and after 7 weeks of HIIT (POST). Tissues were analysed for proteolysis markers, and in vitro experiments were performed to provide additional insights. Atrogene mRNAs (TRIM63, FBXO32, FOXO3A) were upregulated at POST versus both PRE and MID (P < 0.05). 20S proteasome core protein abundance increased at POST versus PRE (P = 0.031) and MID (P = 0.049). 20S proteasome activity, and protein levels for calpain‐2 and Beclin‐1 increased at MID and POST versus PRE (P < 0.05). Ubiquitinated proteins showed model significance (P = 0.019) with non‐significant increases at MID and POST (P > 0.05). in vitro experiments recapitulated the training phenotype when stimulated with a hypertrophic stimulus (insulin‐like growth factor 1; IGF1) followed by a subsequent AMP‐activated protein kinase activator (5‐aminoimidazole‐4‐carboxamide ribonucleotide; AICAR), as demonstrated by larger myotube diameter in IGF1‐treated cells versus IGF1 followed by AICAR treatments (I+A; P = 0.017). Muscle protein synthesis (MPS) levels were also greater in IGF1‐treated versus I+A myotubes (P < 0.001). In summary, the loss in RT‐induced VL CSA with HIIT coincided with increases in several proteolytic markers, and sustained proteolysis may have driven this response. Moreover, while not measured in humans, we interpret our in vitro data to suggest that (unlike RT) HIIT does not stimulate MPS. New Findings: What is the central question of this study?Determining if HIIT‐induced reductions in muscle hypertrophy following a period of resistance training coincided with increases in proteolytic markers.What is the main finding and its importance?Several proteolytic markers were elevated during the HIIT training period implying that increases in muscle proteolysis may have played a role in HIIT‐induced reductions in muscle hypertrophy. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF) binding to endothelial TNF receptor-I (TNFR-I) facilitates monocyte recruitment and chronic inflammation, leading to the development of atherosclerosis. In vitro data show a heightened inflammatory response and atherogenic potential in endothelial cells (ECs) from African American (AA) donors. High laminar shear stress (HSS) can mitigate some aspects of racial differences in endothelial function at the cellular level. We examined possible racial differences in TNF-induced monocyte adhesion and TNFR1 signaling complex expression/activity, along with the effects of HSS. Tohoku Hospital Pediatrics-1 (THP-1) monocytes were used in a co-culture system with human umbilical vein ECs (HUVECs) from Caucasian American (CA) and AA donors to examine racial differences in monocyte adhesion. An in vitro exercise mimetic model was applied to investigate the potential modulatory effect of HSS. THP-1 adherence to ECs and TNF-induced nuclear factor kappa B (NF-κB) DNA binding were elevated in AA ECs compared to CA ECs, but not significantly. We report no significant racial differences in the expression of the TNFR-I signaling complex. Application of HSS significantly increased the expression and shedding of TNFR-I and the expression of TRAF3, and decreased the expression of TRAF5 in both groups. Our data does not support TNF-induced NF-κB activation as a potential mediator of racial disparity in this model. Other pathways and associated factors activated by the TNFR1 signaling complex are recommended targets for future research. [ABSTRACT FROM AUTHOR]

We investigated the effects of performing a period of resistance training (RT) on the performance and molecular adaptations to a subsequent period of endurance training (ET). Twenty‐five young adults were divided into an RT+ET group (n = 13), which underwent 7 weeks of RT followed by 7 weeks of ET, and an ET‐only group (n = 12), which performed 7 weeks of ET. Body composition, endurance performance and muscle biopsies were collected before RT (T1, baseline for RT+ET), before ET (T2, after RT for RT+ET and baseline for ET) and after ET (T3). Immunohistochemistry was performed to determine fibre cross‐sectional area (fCSA), myonuclear content, myonuclear domain size, satellite cell number and mitochondrial content. Western blots were used to quantify markers of mitochondrial remodelling. Citrate synthase activity and markers of ribosome content were also investigated. RT improved body composition and strength, increased vastus lateralis thickness, mixed and type II fCSA, myonuclear number, markers of ribosome content, and satellite cell content (P < 0.050). In response to ET, both groups similarly decreased body fat percentage (P < 0.0001) and improved endurance performance (e.g. V̇O2max${\dot V_{{{\mathrm{O}}_2}\max }}$, and speed at which the onset of blood lactate accumulation occurred, P < 0.0001). Levels of mitochondrial complexes I–IV in the ET‐only group increased 32–66%, while those in the RT+ET group increased 1–11% (time, P < 0.050). Additionally, mixed fibre relative mitochondrial content increased 15% in the ET‐only group but decreased 13% in the RT+ET group (interaction, P = 0.043). In conclusion, RT performed prior to ET had no additional benefits to ET adaptations. Moreover, prior RT seemed to impair mitochondrial adaptations to ET. Key points: Resistance training is largely underappreciated as a method to improve endurance performance, despite reports showing it may improve mitochondrial function.Although several concurrent training studies are available, in this study we investigated the effects of performing a period of resistance training on the performance and molecular adaptations to subsequent endurance training.Prior resistance training did not improve endurance performance and impaired most mitochondrial adaptations to subsequent endurance training, but this effect may have been a result of detraining from resistance training. [ABSTRACT FROM AUTHOR]

Limited research exists examining how resistance training to failure affects applied outcomes and single motor unit characteristics in previously trained individuals. Herein, resistance‐trained adults (24 ± 3 years old, self‐reported resistance training experience was 6 ± 4 years, 11 men and 8 women) were randomly assigned to either a low‐repetitions‐in‐reserve (RIR; i.e., training near failure, n = 10) or high‐RIR (i.e., not training near failure, n = 9) group. All participants implemented progressive overload during 5 weeks where low‐RIR performed squat, bench press, and deadlift twice weekly and were instructed to end each training set with 0–1 RIR. high‐RIR performed identical training except for being instructed to maintain 4–6 RIR after each set. During week 6, participants performed a reduced volume‐load. The following were assessed prior to and following the intervention: (i) vastus lateralis (VL) muscle cross‐sectional area (mCSA) at multiple sites; (ii) squat, bench press, and deadlift one‐repetition maximums (1RMs); and (iii) maximal isometric knee extensor torque and VL motor unit firing rates during an 80% maximal voluntary contraction. Although RIR was lower in the low‐ versus high‐RIR group during the intervention (p < 0.001), total training volume did not significantly differ between groups (p = 0.222). There were main effects of time for squat, bench press, and deadlift 1RMs (all p‐values < 0.05), but no significant condition × time interactions existed for these or proximal/middle/distal VL mCSA data. There were significant interactions for the slope and y‐intercept of the motor unit mean firing rate versus recruitment threshold relationship. Post hoc analyses indicated low‐RIR group slope values decreased and y‐intercept values increased after training suggesting low‐RIR training increased lower‐threshold motor unit firing rates. This study provides insight into how resistance training in proximity to failure affects strength, hypertrophy, and single motor unit characteristics, and may inform those who aim to program for resistance‐trained individuals. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the effects of sub-chronic high fat, high sucrose diet (also termed 'Westernized diet' or WD) feeding on the liver transcriptome during early nonalcoholic fatty liver disease (NAFLD) development.Methods: Brown Norway male rats (9 months of age) were randomly assigned to receive ad libitum access to a control (CTL; 14 % kcal fat, 1.2 % sucrose by weight) diet or WD (42 % kcal from fat, 34 % sucrose by weight) for 6 weeks.Results: Six weeks of WD feeding caused hepatic steatosis development as evidenced by the 2.25-fold increase in liver triacylglycerol content, but did not induce advanced liver disease (i.e., no overt inflammation or fibrosis) in adult Brown Norway rats. RNA deep sequencing (RNA-seq) revealed that 94 transcripts were altered in liver by WD feeding (46 up-, 48 down-regulated, FDR < 0.05). Specifically, the top differentially regulated gene network by WD feeding was 'Lipid metabolism, small molecular biochemistry, vitamin and mineral metabolism' (Ingenuity Pathway Analysis (IPA) score 61). The top-regulated canonical signaling pathway in WD-fed rats was the 'Superpathway of cholesterol biosynthesis' (10/29 genes regulated, p = 1.68E-17), which coincides with a tendency for serum cholesterol levels to increase in WD-fed rats (p = 0.09). Remarkably, liver stearoyl-CoA desaturase (Scd) mRNA expression was by far the most highly-induced transcript in WD-fed rats (approximately 30-fold, FDR = 0.01) which supports previous literature underscoring this gene as a crucial target during NAFLD development.Conclusions: In summary, sub-chronic WD feeding appears to increase hepatic steatosis development over a 6-week period but only induces select inflammation-related liver transcripts, mostly acute phase response genes. These findings continue to outline the early stages of NAFLD development prior to overt liver inflammation and advanced liver disease. [ABSTRACT FROM AUTHOR]

Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving trained college-aged men (n = 11) performing two resistance exercise bouts in a randomized and crossover fashion. The lower-load bout (30 Fail) consisted of 8 sets of lower body exercises to volitional fatigue using 30% one-repetition maximum (1 RM) loads, whereas the higher-load bout (80 Fail) consisted of the same exercises using 80% 1 RM loads. Vastus lateralis muscle biopsies were collected prior to (PRE), 3 h, and 6 h after each exercise bout, and 58 genes associated with skeletal muscle hypertrophy were manually interrogated from our prior microarray data. Select targets were further interrogated for associated protein expression and phosphorylation induced-signaling events. Although none of the 58 gene targets demonstrated significant bout x time interactions, ~57% (32 genes) showed a significant main effect of time from PRE to 3 h (15↑ and 17↓, p < 0.01), and ~26% (17 genes) showed a significant main effect of time from PRE to 6 h (8↑ and 9↓, p < 0.01). Notably, genes associated with the myostatin (9 genes) and mammalian target of rapamycin complex 1 (mTORC1) (9 genes) signaling pathways were most represented. Compared to mTORC1 signaling mRNAs, more MSTN signaling-related mRNAs (7 of 9) were altered post-exercise, regardless of the bout, and RHEB was the only mTORC1-associated mRNA that was upregulated following exercise. Phosphorylated (phospho-) p70S6K (Thr389) (p = 0.001; PRE to 3 h) and follistatin protein levels (p = 0.021; PRE to 6 h) increased post-exercise, regardless of the bout, whereas phospho-AKT (Thr389), phospho-mTOR (Ser2448), and myostatin protein levels remained unaltered. These data continue to suggest that performing resistance exercise to volitional fatigue, regardless of load selection, elicits similar transient mRNA and signaling responses in skeletal muscle. Moreover, these data provide further evidence that the transcriptional regulation of myostatin signaling is an involved mechanism in response to resistance exercise. [ABSTRACT FROM AUTHOR]

We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower load (LL) versus higher load (HL) resistance exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 h, and 6 h after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were significantly greater during the 30 Fail versus 80 Fail (p < 0.001), although total training volume (sets × reps × load) was not significantly different between bouts (p = 0.571). Regardless of bout, more CpG site methylation changes were observed at 3 h versus 6 h post exercise (239,951 versus 12,419, respectively; p < 0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3 h and 6 h following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3 h versus 6 h following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 h following exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 h following exercise (65% and 82%, respectively). While 30 Fail decreased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar between bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to "Focal adhesion," "MAPK signaling," and "PI3K-Akt signaling" were significantly affected at the 3 h and 6 h time points, and again this was regardless of bout. In conclusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts. [ABSTRACT FROM AUTHOR]

We investigated the effects of aging and long‐term physical activity on markers of mitochondrial function and dynamics in the cortex and cerebellum of female rats. Additionally, we interrogated markers of oxidative damage and antioxidants. Thirty‐four female Lewis rats were separated into three groups. A young group (YNG, n = 10) was euthanized at 6 months of age. Two other groups were aged to 15 months and included a physical activity group (MA‐PA, n = 12) and a sedentary group (MA‐SED, n = 12). There were no age effects for any of the variables investigated, except for SOD2 protein levels in the cortex (+6.5%, p = 0.012). Long‐term physical activity increased mitochondrial complex IV activity in the cortex compared to YNG (+85%, p = 0.016) and MA‐SED (+82%, p = 0.023) and decreased carbonyl levels in the cortex compared to YNG (−12.49%, p = 0.034). Our results suggest that the mitochondrial network and redox state of the brain of females may be more resilient to the aging process than initially thought. Further, voluntary wheel running had minimal beneficial effects on brain markers of oxidative damage and mitochondrial physiology. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Do changes in myofibre cross‐sectional area, pennation angle and fascicle length predict vastus lateralis whole‐muscle cross‐sectional area changes following resistance training?What is the main finding and its importance?Changes in vastus lateralis mean myofibre cross‐sectional area, fascicle length and pennation angle following a period of resistance training did not collectively predict changes in whole‐muscle cross‐sectional area. Despite the limited sample size in this study, these data reiterate that it remains difficult to generalize the morphological adaptations that predominantly drive tissue‐level vastus lateralis muscle hypertrophy. Myofibre hypertrophy during resistance training (RT) poorly associates with tissue‐level surrogates of hypertrophy. However, it is underappreciated that, in pennate muscle, changes in myofibre cross‐sectional area (fCSA), fascicle length (Lf) and pennation angle (PA) likely coordinate changes in whole‐muscle cross‐sectional area (mCSA). Therefore, we determined if changes in fCSA, PA and Lf predicted vastus lateralis (VL) mCSA changes following RT. Thirteen untrained college‐aged males (23 ± 4 years old, 25.4 ± 5.2 kg/m2) completed 7 weeks of full‐body RT (twice weekly). Right leg VL ultrasound images and biopsies were obtained prior to (PRE) and 72 h following (POST) the last training bout. Regression was used to assess if training‐induced changes in mean fCSA, PA and Lf predicted VL mCSA changes. Correlations were also performed between PRE‐to‐POST changes in obtained variables. Mean fCSA (+18%), PA (+8%) and mCSA (+22%) increased following RT (P < 0.05), but not Lf (0.1%, P = 0.772). Changes in fCSA, Lf and PA did not collectively predict changes in mCSA (R2= 0.282, adjusted R2= 0.013, F3,8 = 1.050, P = 0.422). Moderate negative correlations existed for percentage changes in PA and Lf (r = −0.548, P = 0.052) and changes in fCSA and Lf (r = −0.649, P = 0.022), and all other associations were weak (|r| < 0.500). Although increases in mean fCSA, PA and VL mCSA were observed, inter‐individual responses for each variable and limitations for each technique make it difficult to generalize the morphological adaptations that predominantly drive tissue‐level VL muscle hypertrophy. However, the small subject pool is a significant limitation, and more research in this area is needed. [ABSTRACT FROM AUTHOR]

We sought to determine the effects of long-term voluntary wheel running on markers of long interspersed nuclear element-1 (L1) in skeletal muscle, liver, and the hippocampus of female rats. In addition, markers of the cGAS-STING DNA-sensing pathway that results in inflammation were interrogated. Female Lewis rats (n = 34) were separated into one of three groups including a 6-mo- old group to serve as a young comparator group (CTL, n = 10), a group that had access to a running wheel for voluntary wheel running (EX, n = 12), and an age-matched group that did not (SED, n = 12). Both SED and EX groups were carried out from 6 mo to 15 mo of age. There were no significant differences in L1 mRNA expression for any of the tissues between groups. Methylation of the L1 promoter in the soleus and hippocampus was significantly higher in SED and EX than in CTL group (P < 0.05). ORF1p expression was higher in older SED and EX rats than in CTL rats for every tissue (P < 0.05). There were no differences between groups for L1 mRNA or cGAS-STING pathway markers. Our results suggest there is an increased ORF1 protein expression across tissues with aging that is not mitigated by voluntary wheel running. In addition, although previous data imply that L1 methylation changes may play a role in acute exercise for L1 RNA expression, this does not seem to occur during extended periods of voluntary wheel running. [ABSTRACT FROM AUTHOR]

We examined if 8 weeks of whey protein (WP) supplementation improved body composition and performance measures in NCAA Division III female basketball players. Subjects were assigned to consume 24 g WP ( n = 8; age, 20 ± 2 years; height, 170 ± 6 cm; weight, 66.0 ± 3.1 kg) or 24 g of maltodextrin (MD) ( n = 6; age, 21 ± 3 years; height, 169 ± 6 cm; weight, 68.2 ± 7.6 kg) immediately prior to and following training (4 days/week anaerobic and resistance training) for 8 weeks. Prior to (T1) and 8 weeks following supplementation (T2), subjects underwent dual X-ray absorptiometry body composition assessment as well as performance tests. The WP group gained lean mass from T1 to T2 (+1.4 kg, p = 0.003) whereas the MD group trended to gain lean mass (+0.4 kg, p = 0.095). The WP group also lost fat mass from T1 to T2 (-1.0 kg, p = 0.003) whereas the MD group did not (-0.5 kg, p = 0.41). The WP group presented greater gains in 1-repetition maximum (1RM) bench press (+4.9 kg) compared with the MD group (+2.3 kg) ( p < 0.05). Moreover, the WP group improved agility from T1 to T2 ( p = 0.001) whereas the MD group did not ( p = 0.38). Both groups equally increased leg press 1RM, vertical jump, and broad jump performances. This study demonstrates that 8 weeks of WP supplementation improves body composition and select performance variables in previously trained female athletes. [ABSTRACT FROM AUTHOR]

Objective: Long INterspersed Element-1 (L1) is an autonomous transposable element in the genome. L1 transcripts that are not reverse transcribed back into the genome can accumulate in the cytoplasm and activate an inflammatory response via the cyclic GMP-AMP (cGAS)-STING pathway. We examined skeletal muscle L1 markers as well as STING protein levels in 10 older individuals (63 ± 11 y, BMI = 30.2 ± 6.8 kg/m2) with end-stage osteoarthritis (OA) undergoing total hip (THA, n = 4) or knee (TKA, n = 6) arthroplasty versus 10 young, healthy comparators (Y, 22 ± 2 y, BMI = 23.2 ± 2.5 kg/m2). For OA, muscle was collected from surgical (SX) and contralateral (CTL) sides whereas single vastus lateralis samples were collected from Y. Results: L1 mRNA was higher in CTL and SX compared to Y (p < 0.001 and p = 0.001, respectively). Protein expression was higher in SX versus Y for ORF1p (p = 0.002) and STING (p = 0.022). While these data are preliminary due to limited n-sizes and the lack of a BMI-matched younger control group, higher L1 mRNA expression, ORF1p and STING protein are evident in older versus younger adults. More research is needed to determine whether cGAS-STING signaling contributes to heightened muscle inflammation during aging and/or OA. [ABSTRACT FROM AUTHOR]

Purpose: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state.Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period.There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged.Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.Methods: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state.Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period.There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged.Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.Results: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state.Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period.There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged.Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.Conclusion: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state.Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period.There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged.Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers. [ABSTRACT FROM AUTHOR]