bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of Inspiratory Muscle Training Between Athletes and Performing Artists
Authors: Winkler Jenna V. , Bunker Aaron K.
Published: June 2021

The purpose of this study was to examine whether inspiratory muscle training (IMT) had differential effects between athletes and performing artist's diaphragm performance. It was hypothesized that the performing artists would experience greater improvements in diaphragm performance than the athletes following an IMT program. The two groups underwent IMT by breathing through an IMT device 2 times every day for 9–11 weeks at 50% of their maximal inspiratory pressure (IP) for 30 seconds. Following IMT there was a significant increase (p<0.05) in maximal IP for athletes (2.7 mmHg or a 24% increase) and performing artists (5.8 mmHg or a 28.5% increase) compared to the control group (1.8 mmHg or a 13.1% increase). No significant difference in maximal expiratory flow rate (EFR) was observed between the groups or compared to controls. While athletes and performing artists both experienced significant improvements in diaphragm performance following the IMT program compared to the control group, no significant difference was observed between the groups for their percent change in IP or EFR. These results show that the magnitude of the effect of the IMT program between athletes and performing artists was equal. The data suggests that performing artists' diaphragm performance responds similarly to athletes' following a IMT program, which is likely due to regular use of their respiratory muscles when practicing for performances

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Left ventricular systolic function is improved in well‐healed burn survivors after six months of exercise training
Authors: Moralez Gilbert , Hieda Michinari , Sarma Satyam , Romero Steven A. , Cramer Matthew N. , Huang Mu , Crandall Craig G.
Published: June 2021

Recent studies have identified that well‐healed burn survivors have altered resting cardiac responses that persist years after the initial burn injury. In healthy non‐burned individuals, prolonged exercise leads to beneficial cardiac remodeling and improved cardiac function. However, it is unknown whether burn survivors likewise demonstrate beneficial cardiac adaptations to long‐term aerobic exercise training. The purpose of this study was to test the hypothesis that six months of aerobic exercise training improves left ventricular systolic function in well‐healed burn survivors. Eleven participants (8 males; aged 43 ± 13 years) with well‐healed burn injuries covering an average total body surface area of 53 ± 25% (range: 22–88%), participated in a progressive 6‐month aerobic‐focused exercise training regimen. An index of cardiac systolic function was assessed via speckle tracking analysis to measure local longitudinal peak systolic strain (Tomtec software) at rest, prior to and after the 6‐month aerobic‐focused exercise training regimen. Exercise training improved resting left ventricular longitudinal systolic strain (Pre, −13.6 ± 2.9% vs. Post, −16.3 ± 2.9%, P=0.013). These data show that despite impaired resting cardiac responses that persist well past complete recovery, cardiovascular adaptations to long‐term aerobic exercise training can be obtained in well‐healed burned subjects.

Support or Funding Information

Work funded by NIH GM068865

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Exercise Training on Sympathetic Vasoconstrictor Responsiveness and Sympatholysis in Female Rats
Authors: DeLorey Darren S. , Just Timothy P. , Cooper Ian R. , Liu Sixue
Published: June 2021

Our laboratory has previously reported that aerobic exercise training enhances contraction‐mediated inhibition of sympathetic vasoconstriction (sympatholysis) in male rats. Whether aerobic exercise training has a similar effect in female rats has not been established. Therefore, the purpose of the present study was to investigate the hypothesis that aerobic exercise training would blunt sympathetic vasoconstrictor responsiveness and enhance sympatholysis in female rats. Female Sprague‐Dawley rats were randomly assigned to sedentary (n=10) or treadmill exercise training (n=8) groups (15 min at 40 m/min, 5% gradient; 5 d/week) for 10 weeks. Following the completion of the sedentary behavior or exercise training intervention, rats were anaesthetized and instrumented for stimulation of the lumbar sympathetic chain and the measurement of arterial blood pressure and femoral vascular conductance (FVC). The triceps surae muscle group was stimulated to contract rhythmically at 60% of maximal contractile force. The percentage change of FVC (Δ%FVC) in response to sympathetic stimulation delivered at 2 and 5 Hz was determined at rest and during contraction. At rest, sympathetic vasoconstrictor responsiveness (Δ%FVC) was not different (p>0.05) between sedentary and exercise trained rats in response to sympathetic stimulation delivered at 2Hz (Sedentary: −39 ± 12 %; Exercise Trained: −45 ± 9 %) and 5Hz (Sedentary: −57 ± 8 %; Exercise Trained: −61 ± 9 %). Muscle contraction blunted (p<0.05) sympathetic vasoconstrictor responsiveness in both sedentary and exercise trained rats and the magnitude of sympatholysis was not different (p>0.05) between sedentary (2Hz: 24 ± 8 %; 5Hz: 29 ± 10 %) and exercise‐trained (2Hz: 30 ± 10 %; 5Hz: 29 ± 13 %) rats. These data demonstrate that aerobic exercise training does not alter sympathetic vasoconstrictor responsiveness or contraction mediated inhibition of sympathetic vasoconstriction (sympatholysis) in female rats. Further investigation is required to determine why female rats respond differently to exercise training than male rats.

Support or Funding Information

Natural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation, and Alberta Advanced Education and Technology.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lower Extremity Resistance Training Enhances Balance Ability in Patients with Hemiparesis
Authors: Liu Huang‐Chun , Chen Chia‐Pei , Han Der‐Sheng , Wang Jong‐Shyan
Published: June 2021

Balance ability is an important influencing factor of the quality of life in patients with hemiparesis. This study was aimed at investigating the effects of lower extremity resistance training (LERT) on the balance ability in patients with hemiparesis. Thirty‐five patients with hemiparesis participated, with a mean age of 54.3 ± 17.9 years. The participants received resistance training for 18 weeks, twice per week, using lower extremity pneumatic resistance machines. The results demonstrated that LERT significantly improved muscle strength (p < .01) and power (p < .01) in patients with hemiparesis. This training also caused a significant increase in Berg balance scale (BBS) score (p < .05). Moreover, BBS score positively correlated with lower extremity muscle strength in terms of leg press (r = .54, p = .007), knee extension (r = .56, p = .004), and knee curl (r = .49, p = .014), and with lower extremity muscle power in terms of leg press (r = .51, p = .002) and knee extension (r = .44, p = .009). No statistically significant difference was observed in knee curl following LERT. Therefore, we conclude that LERT improves the balance ability, which may be considered as routine training option for patients with hemiparesis.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Can Six‐Weeks of Whole‐Body Resistance Training Improve Endothelial Function in Older Adults?
Authors: O'Brien Myles William , Robinson Susan , Evans Kailey , Mekary Said , Kimmerly Derek
Published: June 2021

Aerobic exercise training improves peripheral vascular function in older adults. However, it is unclear whether resistance training (RT) has similar benefits on vascular health in this population. Additionally, there is a paucity of research evaluating the influence of RT on vascular function in lower‐limb arteries, which are more susceptible to the development of atherosclerosis. Our aim was to determine if RT improves upper‐ and/or lower‐limb vascular endothelial function in older adults. We assessed vascular function in 8 older adults (2♂, 66±8 years, BMI, 26.3±3.6 kg/m2) before and after six‐weeks of whole‐body RT. The supervised RT program was conducted 3 days/week and consisted of 8 exercises working all major muscle groups for 2 sets of 10 repetitions. Vascular endothelial function was assessed using high‐resolution duplex ultrasonography via the flow‐mediated dilation (FMD) technique in both the brachial (BA) and popliteal arteries (PA). Nitroglycerin‐mediated dilation (NMD, 0.4 mg sublingual spray) was assessed in the PA as a measure of endothelial‐independent function. Muscular fitness was assessed via maximal grip strength and the 30‐second sit to stand test. Following the RT program, BA‐FMD increased (p=0.04) from 4.6±1.3% to 6.6±2.2% without a corresponding change (p>0.05) in PA‐FMD (2.2±1.7% to 2.8±1.8%). However, there was a large effect size determined for PA‐FMD (d=2.1) and the overall absolute PA‐FMD increased by 26% (0.156±0.140 mm to 0.204±0.150 mm; p>0.05). No differences were observed in resting BA and PA diameters, nor in PA‐NMD (all p>0.05). Following RT, no BMI or muscular fitness changes were observed (p>0.05). Short‐term whole‐body RT induces favorable outcomes in upper limb vascular function in older adults, without parallel improvements in the lower‐limb. This latter finding suggests that a longer RT intervention may be required to augment lower‐limb vascular health in older adults. Independent of changes in BMI or muscular strength, RT appears be an effective intervention for combating age‐associated declines in upper limb endothelial function, which in turn, may decrease their risk of developing cardiovascular diseases.

Support or Funding Information

Support provided by: Canadian Foundation for Innovation: Leaders Opportunity Fund, Faculty of Health Professions Research Development, and Nova Scotia Health Research Foundation Development/Innovation grants. SAR and MWO were recipients of a Nova Scotia Graduate Scholarship. MWO was awarded a Nova Scotia Health Research Foundation Scotia Scholar Award and a Heart & Stroke BrightRed Award.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
AFTER EFFECTS OF A SINGLE BOAT OF AEROBIC EXERCISE IN THE HEMODYNAMIC AND AUTONOMIC VARIABLES IN STAGE 3 CHRONIC KIDNEY DISEASE PATIENTS
Authors: Rezende Rafael Andrade , Pinto Walter Pereira , Dalboni Maria Aparecida , Tinucci Tais
Published: June 2021

Introduction

The prevalence of chronic kidney disease (CKD) has increased exponentially in recent years mostly due to hypertension and diabetes. Effective treatment of these diseases is important in slowing the progression of CKD. An important tool to improve blood pressure (BP) control is physical exercise. Physical training consistently decreases the BP of hypertensive individuals. In addition, it is known that physical training improves cardiac autonomic modulation efficiently. Acute physical exercise promotes post‐exercise hypotension (PEH) and improves cardiac autonomic modulation. Thus the aim of the study was to evaluate the effect of an acute session of aerobic exercise on blood pressure and on the autonomic cardiac modulation of stage 3 CKD patients.

Methods

16 volunteers, being 8 CKD, 53 ± 7 years; creatinine clearance 49 ± 9 ml/min; Systolic BP 127 ± 6 mmHg; Diastolic BP 79 ± 8 mmHg) and 8 controls (CON), 50 ± 7 years; Systolic BP: 112 ± 10 mmHg; Diastolic BP 75 ± 5 mmHg, performed 2 experimental sessions. An aerobic exercise session on cycle ergometer, 45 minutes at 50% VO2peak and a 45‐minute session at rest. The sessions were held at random. The auscultatory measurements of BP and heart rate (HR) measurements by palpation of the radial artery were performed before and after the interventions. Descriptive data analysis (mean and standard deviation), two‐factor ANOVA (group × moment), and calculation of the actual effect of exercise [(Δ exercise) − (Δ control)] were performed with P <0.05.

Results

Exercise decreased systolic BP (CKD −13 ± 3 and CON −7 ± 2), diastolic BP (−9 ± 4 and 3 ± 1) and increased HR (3 ± 2 and 8 ± 8). In cardiac autonomic modulation there was no significant difference between the two groups.

Discussion and Conclusions

Patients with CKD have a higher mean systolic BP decrease and a lower HR increase after an acute aerobic exercise session when compared with healthy subjects. No differences were observed in diastolic BP, mean BP and cardiac autonomic modulation

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High intensity walking time is a key determinant to increase VO2peak after 5‐month interval walking training in middle‐aged and older people
Authors: Masuki Shizue , Morikawa Mayuko , Nose Hiroshi
Published: June 2021

Background and hypothesis

It has been suggested that a substantive proportion of participants in exercise training program showed no increase in peak aerobic capacity (VO2peak) even after the same period of training as those who showed a significant increase in VO2peak. We examined the hypothesis that this would be caused by an inter‐individual variation in exercise intensity relative to individual VO2peak for training.

Methods

Middle‐aged and older men and women (n=696, aged 65±7(SD) years) participated in the study. They were instructed to perform interval walking training (IWT) to repeat ≥5 sets of fast and slow walking for 3 min each at ≥70% and 40% VO2peak for walking, respectively, per day ≥4 days/wk for 5 months, during which period exercise intensity and time were measured with a portable calorimeter every min and the measurements were transferred to a sever computer via the internet every 2 weeks.

Results

The average fast, slow, and total walking time during IWT for 5 months were 87±65(SD), 99±87, and 186±126 min/week, respectively. After training, VO2peak increased by 2.9±3.9(SD) ml/kg/min on average. When we analyzed the relationship between the increase in VO2peak from the baseline and the fast, slow, and total walking time per week during IWT, respectively, we found that the increase in VO2peak was in proportion to the fast walking time in the range of 0 to 50 min/week (R2=0.92, P<0.001), but above the range, it reached the steady level of 3.6 ml/kg/min. In contrast, the increase in VO2peak after training was not significantly correlated with either slow (P=0.06) or total walking time (P=0.3) during IWT for 5 months.

Conclusion

High intensity walking time during IWT is a key determinant to increase VO2peak in middle‐aged and older people.

Support or Funding Information

This study was supported by a grant from the Japan Society for the Promotion of Science (15H04680).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Amniotic membrane improves force production after repair of a massive rotator cuff tear
Authors: Kepple Jeffrey W. , Saad Maarouf , Claflin Dennis R. , Kovacevic David , Mendias Christopher L.
Published: June 2021

Rotator cuff tears are a common cause of upper extremity disability, with nearly 250,000 surgical repairs performed annually. Chronically torn rotator cuff muscles display profound muscle atrophy, fibrosis and accumulation of fat in and around muscle fibers. Even after undergoing surgical repair, many patients continue to have persistent muscle atrophy, and re‐tear rates are 40% or more. Identifying novel therapies that can promote muscle regeneration after rotator cuff repair could lead to substantial improvements in our ability to treat chronic rotator cuff tears. Human amniotic‐derived grafts are a type of allograft that is thought to have the potential to improve tissue regeneration, although the mechanism of these products is not well characterized and to our knowledge has not been studied in respect to rotator cuff regeneration. Using a preclinical rotator cuff tear model in rats, our objective was to determine the efficacy of human amniotic derived grafts on rotator cuff muscle regeneration. To accomplish this, we induced a chronic rotator cuff tear for 30 days and then repaired the tear in the presence or absence of the human amniotic stem cell graft. We then analyzed the contractile function of muscle fibers from control and treated muscles. Muscle cross‐sectional area (CSA), maximum isometric force (Fo) and the force per cross‐sectional area, or specific force (sFo) were recorded from muscle fibers isolated from each of these groups. We hypothesized that treatment with human amniotic cell graft would improve sFo in rats compared to rats without these grafts. The CSA of the amniotic membrane repair group was 53% greater than the control repair group (p<0.01), and the Fo was also 55% higher with membrane supplementation (p<0.01). Further, sFo of the membrane repair group was 13% larger than the control repair (p=0.02). Combined, the augmentation of chronic rotator cuff repair surgery with a human amniotic derived graft in rats markedly improved muscle function. Based on this promising preclinical data, further study of human amniotic stem cell grafts in patients with chronic rotator cuff tears in warranted.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Skeletal Muscle Disuse Alters Exosome miRNA Predicted to Target Various Signaling Pathways Related to Muscle Atrophy
Authors: Van Pelt Douglas W. , Hunt Emily R. , Butterfield Timothy A. , Miller Benjamin F. , Hamilton Karyn L. , Dupont‐Versteegden Esther E.
Published: June 2021

Skeletal muscle atrophy that occurs during disuse is linked to poor functional and metabolic health outcomes. Small noncoding microRNAs (miRNAs) are now appreciated as important components in the regulation of muscle growth and atrophy and can be carried through systemic circulation in exosomes to potentially mediate systemic adaptations. However, little is known about how atrophic conditions influence the miRNA content of exosomes. The purpose of this study was to determine changes in exosome miRNA in response to atrophic conditions. Adult (10 months old) Brown Norway/F344 male rats were subjected to either normal, weight‐bearing conditions (WB: n=7) or a 7‐day hindlimb suspension (HS: n=6) protocol that is known to induce significant skeletal muscle atrophy in select hindlimb muscles. Rats received deuterium oxide (D2O) over 10 days to label newly synthesized proteins for determination of fractional synthesis rate (FSR, %/day). Rat serum was collected and filtered through a 0.22μm filter for removal of larger extracellular vesicles. Exosomes were isolated using the ExoQuick™ Precipitation solution before isolation of the exosome miRNA. As expected, HS had lower myofibrillar skeletal muscle FSR compared with WB rats (0.72 ± 0.09%/day vs 1.64 ± 0.27%/day; p<0.05). MiRNA microarray analysis of exosome miRNA revealed 73 differentially expressed (p<0.05) miRNA between WB and HS conditions. The list of differentially expressed exosome miRNAs was uploaded to DIANA‐miRPath for pathway analysis and prediction of regulatory pathways potentially impacted by the altered exosome miRNAs during atrophy. Various pathways related to muscle protein homeostasis were significantly predicted (p<0.01) to be targeted by the differentially expressed exosome miRNA, including MAPK signaling, focal adhesion, Rap1 signaling, FOXO signaling, ubiquitin mediate proteolysis, TGF‐beta, and mTOR signaling. These data suggest that alterations in systemic exosome miRNA reflect changes in the major pathways dictating muscle atrophy during muscle disuse. In addition, selective packaging and release of exosomes containing miRNA important for regulation of muscle atrophy may be a major contributor to determining skeletal muscle homeostasis during muscle disuse.

Support or Funding Information

NIH grants AT009268 and AG042699

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification and Characterization of F‐Box and Leucine‐Rich Repeat Protein 22 (Fbxl22) in Skeletal Muscle
Authors: Driscoll Julia , Waddell David
Published: June 2021

Skeletal muscle atrophy is a physiological condition that results in decreased muscle size and strength and occurs in response to immobilization, denervation, spinal cord injury and aging. In order to better characterize the molecular genetic events of neurogenic atrophy, the gastrocnemius muscle was isolated from mice following 3 days and 14 days of sciatic nerve denervation. The gene expression profile in the denervated muscle tissue was then analyzed by microarray and compared to control muscle tissue in order to identify novel neurogenic atrophy‐induced genes. The microarray data revealed that F‐Box and Leucine‐Rich Protein 22 (Fbxl22), which has previously been shown to act as an E3 ubiquitin ligase that targets sarcomeric proteins for degradation by the 26S proteasome in cardiac muscle, is also expressed in skeletal muscle and is significantly induced in response to denervation. To confirm that Fbxl22 is expressed in muscle cells, we cloned a novel Fbxl22 intra‐exonic splice variant that codes for a 193 amino acid polypeptide. Additionally, quantitative PCR (qPCR) was used to assess Fbxl22 expression levels in both proliferating and differentiated muscle cells and the results demonstrated that Fbxl22 expression levels are relatively low in proliferating myoblasts, but show significantly elevated expression in differentiated myotubes. In order to characterize the transcriptional regulation of Fbxl22, fragments of the proximal promoter located immediately upstream of the start of transcription were cloned and fused to a reporter gene. The reporter plasmids were then transfected into C2C12 mouse muscle cells in combination with myogenic regulatory factor (MRF) expression plasmids, which resulted in significant activation of reporter gene activity. Furthermore, conserved E‐box elements in the proximal promoter region of the Fbxl22 gene were identified, mutated, and analyzed for their role in the transcriptional regulation of Fbxl22 reporter gene activity. The mutation of the conserved E‐box sequences rendered the Fbxl22 reporter genes inactive, suggesting that these elements are potentially necessary for proper Fbxl22 expression in muscle tissue. The discovery that Fbxl22 is expressed in muscle combined with the observation that this gene, a potential E3 ubiquitin ligase, is induced in response to neurogenic atrophy helps further our understanding of the molecular genetic events of skeletal muscle wasting.

Support or Funding Information

The work was support by University of North Florida Transformational Learning Opportunity grants to D.W.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Impact of Chronic Doxorubicin Administration on Satellite Cell Population and Capillary Density in Multiple Skeletal Muscles
Authors: D'Lugos Andrew C. , Fry Christopher S. , Hale Taben M. , Gonzales Rayna J. , Angadi Siddhartha S. , Carroll Chad C. , Dickinson Jared M.
Published: June 2021

Anthracyclines are mainstay chemotherapeutic agents proven effective at reducing disease recurrence and mortality in breast cancer patients. However, these drugs also have harmful side effects that include skeletal muscle wasting. The purpose of this study was to assess the impact of bi‐weekly doxorubicin (DOX) administration on the satellite cell population and capillary density in multiple skeletal muscles. We hypothesized that DOX treatment would reduce fiber size, along with the satellite cell population and capillary density of the soleus (SOL) and extensor digitorum longus (EDL) muscles. Eight‐week old ovariectomized female Sprague‐Dawley rats were randomized to one of two treatments: DOX and vehicle (Veh). DOX (4 mg/kg) or Veh (saline) intraperitoneal injections were performed bi‐weekly for a total of 3 injections (cumulative dose 12 mg/kg). Animals were euthanized 5d following the last injection, during which the SOL and EDL were dissected and prepared for immunohistochemical analysis. Relative to Veh, cross‐sectional area (CSA) of the SOL and EDL muscle fibers were 30% and 45% smaller, respectively, in DOX (p<0.05 vs. Veh). The satellite cell population and capillary density were 40% and 35% lower, respectively, in the SOL of DOX‐treated versus Veh‐treated rats (p<0.05), whereas the satellite cell population and capillary density in the EDL were unchanged by DOX (p>0.05). Chronic doxorubicin administration is associated with reduced fiber size in multiple skeletal muscles, however doxorubicin appears to impact the satellite cell population and capillary density in a muscle‐specific manner.

Support or Funding Information

Intramural funds from Arizona State University.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigating the Role of mTORC1 in the Androgen‐Mediated Regulation of Skeletal Muscle Growth
Authors: Rossetti Michael L. , Gordon Bradley S.
Published: June 2021

Androgens play an important role in regulating skeletal muscle growth largely through changes in muscle protein balance (synthesis + breakdown). Despite this, the underlying molecular mechanism(s) by which androgens alter protein balance and subsequent muscle growth are poorly defined. Previous research has implicated signaling through the mechanistic target of rapamycin complex 1 (mTORC1) in the androgen‐mediated regulation of protein balance as phosphorylation of mTORC1 substrates that control both protein synthesis and protein breakdown have been shown to be altered by androgen depletion/treatment. However, the role of mTORC1 in the androgen‐mediated regulation of muscle growth in vivo has yet to be defined. To define this role, 10‐week old male mice were randomized into four groups of equal body weight, subjected to a sham or castration surgery, then allowed to recover for 7 weeks to induce muscle atrophy in the castrated groups. Following the recovery, sham and castrated mice were implanted with either a control pellet or a pellet designed to release rapamycin at a rate of ~3 mg/kg of body weight/day over a period of 60 days. One‐week post implantation, a group of castrated mice implanted with either control pellets or rapamycin pellets began receiving weekly, intramuscular injections of nandrolone decanoate (ND) to induce muscle regrowth. All other sham and castrated mice received vehicle only. Mice were treated with vehicle or ND for 6 weeks (42 days). The tibialis anterior (TA) was harvested for analysis. The efficacy of the rapamycin pellets to inhibit mTORC1 was confirmed by the inability of insulin to increase phosphorylation of mTORC1 substrates [i.e. 70 kDa ribosomal protein S6 kinase 1 (Thr389), eIF4E binding protein 1 (Ser65), and uncoordinated like kinase 1(Ser757)] in mice receiving rapamycin even though induction of Akt (Thr308) phosphorylation was unaffected. Castration reduced TA wet weight and muscle fiber cross sectional area (CSA), but these values were restored to sham levels with ND administration, even in the presence of rapamycin. Further, the protein content of the TA was also decreased by castration, and ND administration restored this value to sham levels even in the presence of rapamycin. These changes in protein content were not due to changes in the translational capacity of the muscle as RNA content was similar across treatments. In all, these data indicate that androgens alter protein balance and muscle regrowth in an mTORC1‐independent manner.

Support or Funding Information

Start‐up funds from the University of Central Florida

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sarcopenia‐Associated Plasma Biochemistry of Community‐Based Women Enrolled in a Lifestyle Modification Program
Authors: Barros Layene Peixoto , Kano Hugo Tadashi , Manda Rodrigo Minoru , Bernardino Caroline , Nakagaki Mariana Santoro , Burini Roberto Carlos
Published: June 2021

RATIONALE

Sarcopenia is one of major currently illness associated with contemporary behaviors and having metabolic outcomes yet to be clarified.

PURPOSE

This study aimed to identify demographic, socioeconomic, physical activity and particularly clinical‐biochemical factors associated with muscle mass hypotrophy in community‐based women screened for a lifestyle modification program.

METHODS

Baseline data were analysed from 996 women (55.7 ± 15.9 years old), clinically selected for the “Move for Health” lifestyle modification program during 2005 to 2016. The cross‐sectional analysis had muscle mass as independent variable and the co‐variables demographic, socioeconomic, physical activity, anthropometry, and biochemical data. Muscular Mass Index (kg muscle mass/m2 height =MMI) data was splitted into quartiles for the co‐variables distribution and analysis by Statistica 10.0 software, with p <0.05 as significant.

RESULTS

Women with lower muscle mass (Q1) were older, with incomplete elementary education, low family income, presenting poor perception of health status and classified at the lowest level of weekly physical activity. The lower muscle mass was accompanied by higher values of TG, hs‐CRP, fasting glucose and HOMA‐IR, and lower values of HDL‐col, uric acid, albumin and leukocytes. By 92% of Q1 could be attained by the plasma variables HDL‐col, HOMA‐IR and hs‐CRP, in descending order of magnitude.

CONCLUSION

Muscle hypotrophy of adult female is associated with increased inflammatory and pro‐oxidant markers, characteristics of aging, lower socioeconomic status and low physical activity levels.

Support or Funding Information

Supported by CNPq and CAPES

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Preventive effects of capillary regression on Brazilian honeybee propolis in disused skeletal muscle of rats
Authors: Fujino Hidemi , Kondo Hiroyo , Matsumoto Tomohiro , Ono Kohei , Ikeji Takuya , Takuwa Miho , Hirabayashi Takumi , Ishihara Akihiko
Published: June 2021

PURPOSE

A chronic decrease in activity results in muscle capillary regression that is due, in part, to the overproduction of reactive oxygen species. Brazilian propolis (BP) is natural polyphenol‐rich substance collected by honeybees. The purpose of the present study was to investigate the protective effects of BP supplementation on capillary regression in hindlimb unloading‐induced atrophied soleus muscle.

METHODS

Twenty‐eight male Wistar rats were assigned randomly either to a control, control with BP supplementation, hindlimb unloaded or hindlimb unloaded with BP supplementation group for 14 days. The three‐dimensional capillary network of soleus muscle was visualized using a confocal laser scanning technique. The capillary volume, frequency distribution of luminal diameters and capillary‐to‐fiber ratio were measured. In addition, mojor proangiogenic factors, VEGF, Flt‐1, FlK‐1, anti‐angiogenic factors, thrombospondin‐1, and oxidative stress maker were determined.

RESULTS

The capillary volume, luminal diameter and capillary‐to‐fiber ratio in atrophied muscle were lower than those in control. BP supplementation, however, attenuated the capillary regression under disused muscle. In addition, the expression levels of thrombospondin‐1 and SOD‐1 were decreased and the level of VEGF was increased in BP supplemented muscle. Furthermore, TUNEL‐positive endothelial cells in BP supplemented muscle were decreased although TUNEL‐positive endothelial cells in atrophied muscle were increased.

CONCLUSION

These results suggest that Brazilian propolis supplementation may be an effective treatment to counter the regression of muscle capillary under disuse condition.

Support or Funding Information

Supported by Yamada Research Grant.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Estrogen‐related Receptor α Overexpression Drives a Metabolic and Gene Expression Program Mimicking Aerobic Exercise in Skeletal Muscle
Authors: Huss Janice M. , Hamilton Angelica , Li Jing
Published: June 2021

Aerobic exercise is considered one of the most effective interventions to prevent obesity and type 2 diabetes (T2D). Exercise increases skeletal muscle insulin sensitivity by stimulating mitochondrial respiration and fatty acid oxidation through coordinated regulation of metabolic genes. Transcriptional pathways that regulate exercise‐induced metabolic gene programs present an attractive class of therapeutic targets to combat obesity and related metabolic diseases. We and others have shown that the Estrogen‐related Receptor α (ERRα) nuclear receptor regulates mitochondrial biogenesis, respiration and fatty acid oxidation and is required for metabolic reprogramming in response to exercise training. The objective of these studies is to determine whether ERRα over‐expression is sufficient to mediate exercise‐induced adaptations in muscle. We generated a conditional ERRα transgenic mouse line that expresses the Flag‐tagged human ERRα in skeletal muscle‐specific manner when crossed with Mck‐Cre recombinase mice (ERRαMOE). We examined gene expression (trancript and protein) and characterized the metabolic phentoype of the ERRαMOE mice. ERRαMOE mice exhibited a reddening of the superficial gastrocnemius and quadriceps, characteristic of oxidative muscles, accompanied by a reciprocal change in myosin heavy chain (MHC) IIb (−35%) and IIa (+80%) expression. Mitochondrial content was higher in skeletal muscle and heart, but not in non‐muscle tissues, based on mtDNA quantitation and citrate synthase protein expression. Consistently, basal (+32%) and maximal (+70%) O2 consumption rates were increased in FDB fibers isolated from ERRα‐MOE compared to WT. Signaling through the AMP‐activated kinase (AMPK) pathway, which mediates exercise‐dependent metabolic reprogramming, was unchanged in the basal state; however, maximal activation by AICAR was enhanced in ERRα‐overexpressing myotubes. We assessed systemic glucose homeostasis in adult chow fed mice. Although fasting glucose (6 hr) was slightly lower in ERRαMOE, no significant difference in glucose tolerance was observed. However, the results of insulin tolerance tests showed that ERRαMOE mice were more insulin sensitive than WT. In future studies we will investigate whether ERRα activation in skeletal muscle protects against high fat diet‐induced insulin resistance. Based on the results from these studies, ERRα over‐expression mimics the effects of exercise on skeletal muscle mitochondrial respiratory capacity and improves whole body insulin sensitivity.

Support or Funding Information

Supported by Diabetes and Metabolic Research Institute (DMRI) and Shared Resource Pilot Awards from the City of Hope and NIH U24DK097748

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Autophagy and mitophagy flux in skeletal muscle during chronic‐contractile activity
Authors: Kim Yuho , Triolo Matthew , Erlich Avigail , Lai Jenny , Hood David A.
Published: June 2021

Autophagy and mitophagy are important cellular recycling mechanisms, however the regulation of autophagy and mitophagy flux in training‐induced muscle adaptations remains to be elucidated. Using the microtubule destabilizer colchicine (0.04 mg/kg), this study assessed LC3II and p62 flux in skeletal muscles of Sprague‐Dawley rats (501 ± 9 g) subjected to chronic contractile activity (CCA; 3 hours/day, 9V, 10 Hz continuous, 0.1 ms pulse duration) for 1, 2, 3, 5, and 7 days (N=6–8/group). Colchicine was given via an intraperitoneal injection 48 hours prior to tissue collection, whereas control animals were administered saline as a vehicle treatment. Following 7 days of CCA, there were significant increases in maximal state 3 respiration, accompanied by a decrease in ROS production in IMF mitochondria (P < 0.05), indicating that mitochondrial adaptations were elicited in the stimulated muscle. Notably, whole muscle autophagy flux, as measured by LC3II and p62, was downregulated in response to 3 days of CCA, and further by 7 days of CCA (P < 0.05). In addition, muscle mitochondrial LC3II flux was decreased by 3 days of CCA, indicative of reduced mitophagy. In contrast, the lysosomal system, measured by TFEB and LAMP1 protein levels, was gradually upregulated by CCA, culminating at day 7. Interestingly, the translocation of TFEB into the nucleus in response to CCA was increased at day 3 (P < 0.05). However, this nuclear TFEB was not sustained and subsequently declined back to basal levels. In conclusion, we suggest that chronic exercise can lead to muscle adaptations through a coordinated mechanism, involving a decrease in autophagy/mitophagy flux, combined with an increase in the capacity of the lysosomal system.

Support or Funding Information

This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High Altitude Hypoxia Impacts Omega‐3 Fatty Acid Metabolites in Plasma of Fetal and Newborn Sheep
Authors: Lopez Vanessa , La Frano Michael , Bosviel Remy , Newman John , Thorpe Richard , Feihn Oliver , Zhang Lubo , Wilson Sean M.
Published: June 2021

Perinatal hypoxia has profound effect on an infant's development, with physiological impairment of multiple organ systems. The present study explored the effect of hypoxia due to long term high altitude exposure during gestation and after birth on lipid mediators by measuring the metabolites that foreshadow oxidative stress and inflammation, which are primary drivers of dysfunction. We tested the hypothesis that long term hypoxia reduces the amount of oxylipin and endocannabinoid production, which are important mediators of oxidative stress and inflammation. To test this hypothesis pregnant sheep and newborn lambs were housed at a low altitude (700 m) or exposed to an altitude of 3,800 meters starting gestation day 30. UPLC‐MS/MS analysis was used to investigate the lipid mediator composition in plasma collected from veins of near‐term fetal and newborn animals. The results show that hypoxia causes an overwhelming effect on omega‐3 fatty acids and their derivatives, which are crucial in late‐stage fetal development. Several of the omega‐3 fatty acids reduced with hypoxia have well known effects on inflammation, vascular tone, and oxidative stress. Furthermore, we tracked the origin of the identified oxylipins and endocannabinoids by tracing their pathways. The cytochrome P450 (CYP) pathway enzymes and the subsequent activity of soluble epoxide hydrolase (sEH) are prominent synthesizers of the oxylipins such as epoxyeicosatrienoic acids (EETs) and epoxyoctadecenoic acids (EpOMEs). Previous studies have suggested the role of EETs and EpOMEs in vasodilation, a feature in inflammation. Based on these findings we demonstrated that a majority of the affected oxylipins were produced from CYP and sEH enzymes, which are important to vascular function. These findings provide novel insight into our understanding of lipid metabolites to hypoxia‐induced dysfunction in the developing fetus and newborn. In the long term this may help us develop novel therapies that target inflammatory pathways induced by pre and post‐natal hypoxia.

Support or Funding Information

This material is based upon work supported by NIH grants P01HD083132 and 1U24DK097154 through a pilot project grant to Sean Wilson. VL is a recipient of the American Physiological Society's Short‐Term Research Education Program to Increase Diversity in Health‐Related Research (STRIDE) Fellowship funded by the APS and a grant from the National Heart, Lung and Blood Institute R25HL115473.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sweet Success: Metabolic Substrate Adaptations To Acute Hypoxia In The Naked Mole Rat (Heterocephalus Glaber)
Authors: Pamenter Matthew E. , Kirby Alexia M. , Shuhendler Adam J.
Published: June 2021

Naked mole rats are among the most hypoxia‐tolerant mammals identified. This tolerance is partially achieved through their ability to coordinately reduce metabolic rates by > 85% in acute hypoxia while staying warm and active in their hypoxic underground burrows. Our understanding of the physiological responses that enable their hypoxia‐tolerance is improving; however, the underlying molecular and biochemical mechanisms that support this remarkable energetic suppression are poorly understood. Of particular interest is a putative metabolic fuel substrate switch in hypoxia. Naked mole rats primarily metabolize lipids in normoxia, but carbohydrate metabolism may be favored in hypoxia because carbohydrate oxidation yields more energy per molecule of oxygen than does lipid oxidation. We hypothesized that naked mole rats switch to primarily glucose‐fueled metabolism in acute hypoxia and that the energetic needs of brain and heart are prioritized over those of other tissues. Furthermore, we predicted that heat production from brown adipose tissue, which is a glucose‐intensive process, would be turned off in hypoxia as an energy‐saving strategy. To test these hypotheses, we measured metabolic fuel usage and heat production in naked mole rats exposed to acute hypoxia (7% O2) using non‐invasive in vivo imaging techniques, including infrared thermography, magnetic resonance imaging (MRI), and positron emission tomography (PET). We found that glucose metabolism is markedly upregulated in heart and brain during acute hypoxia, but decreased in liver. Furthermore, heat generation from brown adipose tissue is entirely turned off in hypoxia and the naked mole rat body temperature drops to near or below ambient temperature, indicating that all endogenous heat production ceases in hypoxia. We conclude that naked mole rats maximize the energy/oxygen ratio in their metabolic fuel substrate usage and prioritize feeding the energetic needs of brain and heart over all other metabolic processes in hypoxia.

Support or Funding Information

This study was supported by an NSERC discovery grant to MEP, a CIHR grant to AJS, and CRC grants to MEP and AJS.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Environmental chemicals can disrupt neonatal cardiomyocyte physiology
Authors: Ramadan Manelle , Sherman Meredith , Jaimes Rafael , Swift Luther , Posnack Nikki
Published: June 2021

Background

The ubiquitous nature of plastics has raised concerns pertaining to continuous exposure to plastic polymers and human health risks. Of particular concern is the use of endocrine‐disrupting chemicals in plastic production, including bisphenol A (BPA). Widespread and continuous exposure to BPA can occur through dietary intake, inhalation, dermal and intravenous exposure via consumer products and medical devices. Recent studies have shown a link between BPA exposure and adverse cardiovascular outcomes. This is particularly concerning for vulnerable populations who are at risk of high BPA exposure due to medical treatment, including pediatric patients. Despite significant differences in the cardiac physiology of the developing and adult heart, our current understanding of BPA‐induced cardiac dysfunction has been limited to adult models.

Objective

Cardiac physiology differs significantly between the pediatric and adult heart. We aimed to determine the extent to which BPA exposure contributes to cardiovascular dysfunction, using a neonatal cardiomyocyte model.

Methods

Neonatal rat ventricular myocytes (NRVM) were monitored to assess cell viability, spontaneous beating rate, beat rate variability, and calcium‐handling in the presence of control or bisphenol‐supplemented media. A range of environmental and clinically‐relevant exposure levels were tested [10−9 – 10−5M].

Results

Acute BPA exposure (15 – 20 min) altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability beginning at low concentrations (10−8M BPA). BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes and prolonged calcium transient duration time, which replicated our previously published studies in isolated‐whole hearts. BPA‐induced changes in calcium handling increased the propensity for calcium transient alternans, beginning at low BPA concentrations (10−9M). The observed alterations in calcium kinetics following BPA exposure were not the result of cytotoxicity or altered cell viability.

Conclusion

Our studies show that acute BPA chemical exposure can alter neonatal cardiomyocyte physiology. Additional studies are necessary to determine the effects of bisphenol exposure on pediatric heart electrophysiology and mechanical function, as well as the impact of long‐term treatment that more closely mimics clinical exposure.

Support or Funding Information

This publication was supported by the National Institutes of Health (R00ES023477, UL1TR000075), Children's Research Institute and Children's National Heart Institute.