Running Capacity Research Articles

Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK

SummaryFructose-1,6-bisphosphate (FBP) aldolase links sensing of declining glucose availability to AMPK activation via the lysosomal pathway. However, how aldolase transmits lack of occupancy by FBP to AMPK activation remains unclear. Here, we show that FBP-unoccupied aldolase interacts with and inhibits endoplasmic reticulum (ER)-localized transient receptor potential channel subfamily V, inhibiting calcium release in low glucose. The decrease of calcium at contact sites between ER and lysosome renders the inhibited TRPV accessible to bind the lysosomal v-ATPase that then recruits AXIN:LKB1 to activate AMPK independently of AMP. Genetic depletion of TRPVs blocks glucose starvation-induced AMPK activation in cells and liver of mice, and in nematodes, indicative of physical requirement of TRPVs. Pharmacological inhibition of TRPVs activates AMPK and elevates NAD+ levels in aged muscles, rejuvenating the animals’ running capacity. Our study elucidates that TRPVs relay the FBP-free status of aldolase to the reconfiguration of v-ATPase, leading to AMPK activation in low glucose.

291-OR: Exercise Modulates Glucose Metabolism in Part through Changes in the Gut Microbiome

Exercise is one of the most prescribed interventions in the treatment/prevention of diabetes and metabolic disease. It is well established that different diets affect the distribution of gut microbiota. It has recently been shown that exercise may also modify the gut microbome and these modifications may differ depending on the obesity status of the individual. In this work we investigated whether metabolic changes triggered by exercise are transferable via cecum microbiota transplantationand how this would impact on the obesity response to high fat diet (HFD). Ten-week old, B6J male mice, on chow diet, were reared under either standard sedentary conditions or with access to a running wheel for 4 weeks. Under these conditions the latter mice ran an average of 6 Km per day. Mice were scarified, fecal DNA were sequenced and the cecum microbiota were transplanted into germ-free mice in the presence/absence of HFD. As expected, exercise improved insulin sensitivity and glucose tolerance in the donor mice. Shotgun metagenomic analysis of gut microbiota revealed that exercise was associated with decreased relative abundance of Parasutterella_excrementihominis and Bacteroides_thetaiotaomicron and increased Clostridium clostridioforme CAG:511 and Lactobacillus murinus ASF361. Functional composition of the bacterial metagenome indicated these changes resulted in an upregulation of microbial pathways of valine and methionine metabolism. More importantly, transplant of cecum microbiota from exercised donors to non-exercise donors improved running capacity in lean mice and improved glucose tolerance in mice on HFD. In both groups, this was associated with increased glucose uptake in skeletal muscle soleus and BAT. In summary, exercise reshapes the gut microbiome to improve whole body glucose metabolism, and this effect can be transferred by microbiome transplant. This provides an new opportunity in the treatment of obesity-related insulin resistance. Disclosure B. Brandao: None. M.E. Li: None. W. Cai: None. T.M. Batista: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen Inc., Colgate-Palmolive Company, Medtronic. L.J. Goodyear: None. C. Kahn: Advisory Panel; Self; MedImmune. Board Member; Self; Kaleido Biosciences. Consultant; Self; AntriaBio, Inc., Cobalt Therapeutics, Flagship Pioneering. Research Support; Self; Alnylam. Funding National Institute of Diabetes and Digestive and Kidney Diseases

Blood cardiac biomarkers responses are associated with 24 h ultramarathon performance

PurposeClinical significance of cardiac biomarkers response in ultra-endurance runners are not completely elucidated because events vary in distance/duration and competitors modulate running intensity according to individual running capacity. The aim of this study was to examine the relationship between self-selected exercise intensity with cardiac biomarkers comparing experienced (EXP, N = 11) and novice (NOV, N = 14) runners able to finish a 24h ultramarathon (24UM) with significant differences in performance. MethodsCardiac biomarkers (i.e. CKMB/totalCK, cTnT and NT-proBNP), inflammatory markers (i.e. leukocytes and CRP) and cortisol were analyzed before and after a 24UM. ResultsEXP finished the race with significant (p < 0.05) longer distance than NOV (158.8 ± 15.8 vs 116.8 ± 10.3 Km). Two-way mixed ANOVA showed significant time × performance level interaction with greater increase of cTnT (F(1,23) = 6.18, p = 0.021), NT-proBNP (F(1,23) = 9.27, p = 0.006) and cortisol (F(1, 23) = 5.13, p = 0.03) in the EXP group. CKMB/totalCK (F(1, 23) = 71.90, p < 0.0001) decreased while leukocytes (F(1, 23) = 100.06, p < 0.0001) and CRP (F(1, 23) = 93.37, p < 0.0001) increased in both groups (main effect of time). Correlations were found between 24UM distance and cortisol (r = 0.58; p = 0.002), CKMB (r = 0.47; p = 0.017), cTnT (r = 0.44; p = 0.027) or NT-proBNP (r = 0.56; p = 0.003). Cortisol and NT-proBNP were also significantly correlated (r = 0.51; p = 0.01). ConclusionsAlthough there is no clear evidence of cardiac risk when comparing cardiac biomarkers levels with clinical cut-off values, cardiac biomarkers are associated with running performance and pituitary-adrenocortical system response. In EXP runners, higher levels of cardiac biomarkers and cortisol suggest a more hemodynamically challenged heart during prolonged endurance exercise.

Defective fatty acid oxidation in mice with muscle-specific acyl-CoA synthetase 1 deficiency increases amino acid use and impairs muscle function

Loss of long-chain acyl-CoA synthetase isoform-1 (ACSL1) in mouse skeletal muscle (Acsl1M-/-) severely reduces acyl-CoA synthetase activity and fatty acid oxidation. However, the effects of decreased fatty acid oxidation on skeletal muscle function, histology, use of alternative fuels, and mitochondrial function and morphology are unclear. We observed that Acsl1M-/- mice have impaired voluntary running capacity and muscle grip strength and that their gastrocnemius muscle contains myocytes with central nuclei, indicating muscle regeneration. We also found that plasma creatine kinase and aspartate aminotransferase levels in Acsl1M-/- mice are 3.4- and 1.5-fold greater, respectively, than in control mice (Acsl1flox/flox ), indicating muscle damage, even without exercise, in the Acsl1M-/- mice. Moreover, caspase-3 protein expression exclusively in Acsl1M-/- skeletal muscle and the presence of cleaved caspase-3 suggested myocyte apoptosis. Mitochondria in Acsl1M-/- skeletal muscle were swollen with abnormal cristae, and mitochondrial biogenesis was increased. Glucose uptake did not increase in Acsl1M-/- skeletal muscle, and pyruvate oxidation was similar in gastrocnemius homogenates from Acsl1M-/- and control mice. The rate of protein synthesis in Acsl1M-/- glycolytic muscle was 2.1-fold greater 30 min after exercise than in the controls, suggesting resynthesis of proteins catabolized for fuel during the exercise. At this time, mTOR complex 1 was activated, and autophagy was blocked. These results suggest that fatty acid oxidation is critical for normal skeletal muscle homeostasis during both rest and exercise. We conclude that ACSL1 deficiency produces an overall defect in muscle fuel metabolism that increases protein catabolism, resulting in exercise intolerance, muscle weakness, and myocyte apoptosis.

Dysferlin-deficiency has greater impact on function of slow muscles, compared with fast, in aged BLAJ mice.

Dysferlinopathies are a form of muscular dystrophy caused by gene mutations resulting in deficiency of the protein dysferlin. Symptoms manifest later in life in a muscle specific manner, although the pathomechanism is not well understood. This study compared the impact of dysferlin-deficiency on in vivo and ex vivo muscle function, and myofibre type composition in slow (soleus) and fast type (extensor digitorum longus; EDL) muscles using male dysferlin-deficient (dysf-/-) BLAJ mice aged 10 months, compared with wild type (WT) C57Bl/6J mice. There was a striking increase in muscle mass of BLAJ soleus (+25%) (p<0.001), with no strain differences in EDL mass, compared with WT. In vivo measures of forelimb grip strength and wheel running capacity showed no strain differences. Ex vivo measures showed the BLAJ soleus had faster twitch contraction (-21%) and relaxation (-20%) times, and delayed post fatigue recovery (ps<0.05); whereas the BLAJ EDL had a slower relaxation time (+11%) and higher maximum rate of force production (+25%) (ps<0.05). Similar proportions of MHC isoforms were evident in the soleus muscles of both strains (ps>0.05); however, for the BLAJ EDL, there was an increased proportion of type IIx MHC isoform (+5.5%) and decreased type IIb isoform (-5.5%) (ps<0.01). This identification of novel differences in the impact of dysferlin-deficiency on slow and fast twitch muscles emphasises the importance of evaluating myofibre type specific effects to provide crucial insight into the mechanisms responsible for loss of function in dysferlinopathies; this is critical for the development of targeted future clinical therapies.

Adaptations to high-intensity interval training in skeletal muscle require NADPH oxidase 2

ObjectiveReactive oxygen species (ROS) have been proposed as signaling molecules mediating exercise training adaptation, but the ROS source has remained unclear. This study aimed to investigate if increased NADPH oxidase (NOX)2-dependent activity during exercise is required for long-term high-intensity interval training (HIIT) in skeletal muscle using a mouse model lacking functional NOX2 complex due to absent p47phox (Ncf1) subunit expression (ncf1* mutation). MethodsHIIT was investigated after an acute bout of exercise and after a chronic intervention (3x/week for 6 weeks) in wild-type (WT) vs. NOX2 activity-deficient (ncf1*) mice. NOX2 activation during HIIT was measured using an electroporated genetically-encoded biosensor. Immunoblotting and single-fiber microscopy was performed to measure classical exercise-training responsive endpoints in skeletal muscle. ResultsA single bout of HIIT increased NOX2 activity measured as p47-roGFP oxidation immediately after exercise but not 1 h or 4 h after exercise. After a 6-week HIIT regimen, improvements in maximal running capacity and some muscle training-markers responded less to HIIT in the ncf1* mice compared to WT, including superoxide dismutase 2, catalase, hexokinase II, pyruvate dehydrogenase and protein markers of mitochondrial oxidative phosphorylation complexes. Strikingly, HIIT-training increased mitochondrial network area and decreased fragmentation in WT mice only. ConclusionThis study suggests that HIIT exercise increases NOX2 activity in skeletal muscle and shows that NOX2 activity is required for specific skeletal muscle adaptations to HIIT relating to antioxidant defense, glucose metabolism, and mitochondria.

Animal Modeling for Hologenome: New inbred and conplastic rat exercise models for uncovering crosstalk between nuclear DNA, mitochondrial DNA, and gut microbiota

IntroductionThe hologenome is an ensemble of nuclear DNA (nDNA), mitochondrial DNA (mtDNA), and the microbiome that forms a unit of genetic selection that can propagate from one generation to the next. There is increasing evidence for inherited mitochondria‐gut microbiota involvement in cardiovascular and metabolic diseases. Here, we expand on the selectively‐bred Low Capacity Runner/High Capacity Runner (LCR/HCR) rat exercise model system into a genetically defined rat model framework for studying holobionts in controlled laboratory settings.MethodsAt Generation 23 of selection, we identified extreme representatives of female and male LCR and HCR rats and conducted a series of brother‐sister mating to produce inbred strains‐ LCR/Tol and HCR/Tol. We also developed two conplastic strains, one with nDNA from HCR and mtDNA from LCR, and the other with nDNA from LCR and mtDNA from HCR ‐LCR.HCRmt/Tol and HCR.LCRmt/Tol. mtDNA from LCR/Tol and HCR/Tol strains were compared with publicly available mtDNA from common inbred strains. Rats were phenotyped for cardiovascular risks, which included treadmill exercise capacity, VO2max, echocardiography, and blood pressure (BP) telemetry. Fecal microbial communities were profiled using 16S rRNA sequencing and metatranscriptomics.ResultsAs expected, HCR/Tol had significantly higher exercise capacity compared to LCR/Tol but little effect by mismatched mtDNA suggesting that the nDNA is dominant for regulating aerobic exercise capacity. VO2max measurement confirmed high exercise capacity in HCR/Tol and low in LCR/Tol. LCR mtDNA was identical to mtDNA from Wistar Kyoto inbred strain, while HCR mtDNA was identical to mtDNA from Fischer 344 × Brown Norway F1‐hybrid strain. Consistent with reports from selected LCR HCR rats, LCR/Tol showed significantly increased mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) compared to the HCR/Tol. Transfer of mtDNA from HCR to LCR nDNA background decreased MAP, SBP, DBP, and preserved diastolic cardiac function. In contrast, there was no difference in BP or cardiac parameters between HCR/Tol and HCR.LCRmt/Tol. Microbiome analysis indicated that host genomes co‐inhabit with differential commensal microbiota. Metatranscriptomics showed HCR/Tol had enhanced function in carbohydrate and amino acid metabolism, microbial metabolites production, and stress management.ConclusionWe successfully generated and systematically characterized genotypes and phenotypes of inbred and conplastic LCR/Tol and HCR/Tol animal models for holobiont studies. The inbred and conplastic strains retained key features of LCR HCR selectively bred models ‐‐ some influenced by nDNA‐mtDNA interaction. These models provide for a new pre‐clinical method to explore gut microbiota as therapeutic targets for complex diseases such as hypertension.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ingesting a 12% Carbohydrate-Electrolyte Beverage Before Each Half of a Soccer Match Simulation Facilitates Retention of Passing Performance and Improves High-Intensity Running Capacity in Academy Players.

This study investigated the influence of ingesting a 12% carbohydrate plus electrolyte (CHO-E) solution providing 60g of carbohydrate before each half of a 90-min soccer match simulation (SMS) protocol on skill performance, sprint speed, and high-intensity running capacity. Eighteen elite academy (age: 18 ± 2 years) soccer players ingested two 250-ml doses (pre-exercise and at halftime) of a 12% CHO-E solution or electrolyte placebo administered in a double-blind randomized cross-over design. During an indoor (artificial grass pitch) SMS, dribbling, passing, and sprint performance were assessed, and blood was drawn for glucose and lactate analysis. High-intensity running capacity was assessed following the SMS. Dribbling speed/accuracy and sprint speed remained unchanged throughout the SMS. Conversely, passing accuracy for both dominant (mean percentage difference [95% confidence interval, CI]: 9 [3, 15]) and nondominant (mean percentage difference [95% CI]: 13 [6, 20]) feet was better maintained during the SMS on CHO-E (p < .05), with passing speed better maintained in the nondominant foot (mean percentage difference [95% CI]: 5.3 [0.7, 9.9], p = .032). High-intensity running capacity was greater in CHO-E versus placebo (mean percentage difference [95% CI]: 13 [6, 20], p = .010). Capillary blood glucose concentration was higher in CHO-E than placebo at halftime (CHO-E: 5.8 ± 0.5mM vs. placebo: 4.1 ± 0.4mM, p = .001) and following the high-intensity running capacity test (CHO-E: 4.9 ± 0.4mM vs. placebo: 4.3 ± 0.4mM, p = .001). Ingesting a 12% CHO-E solution before each half of a match can aid in the maintenance of soccer-specific skill performance, particularly on the nondominant foot, and improves subsequent high-intensity running capacity.

Effects of long-term physical exercise on skeletal muscles in senescence-accelerated mice (SAMP8).

We examined the effect of long-term exercise on the prevention of sarcopenia using a senescence-accelerated-prone mice (SAMP8) model. Mice were housed in a wheel cage for 25weeks to increase voluntary exercise. At week 23, endurance running capacity was examined using a treadmill. In a treadmill running test, the wheel cage group had increased endurance running capacity, which suggests that aging-related loss of muscle function was recovered by long-term exercise. Mice were sacrificed and microarray analysis revealed that genes involved in protein synthesis and degradation were upregulated in the skeletal muscles of the wheel cage group, suggesting accelerated protein turnover. Total body and adipose tissue weights decreased following the use of the wheel cage. Thus, long-term, spontaneous physical exercise may assist in recovering from aging-related sarcopenia (loss of muscle function) and obesity.

The Influence of Physical Fitness on Reasons for Academy Separation in Law Enforcement Recruits.

This study analyzed the effects physical fitness may have on reasons for academy separation in law enforcement recruits. A retrospective analysis was conducted on 401 recruits; 330 recruits graduated (GRAD), and 71 recruits separated at various times during academy. Twenty-eight recruits separated for personal reasons (SEPPR); 18 due to physical training failures (i.e., poor fitness) or injury (SEPFI); and 25 due to academic or scenario failures (SEPAS). Fitness testing occurred prior to academy, and included: Push-ups and sit-ups in 60s; a 75-yard pursuit run (75PR); vertical jump; medicine ball throw; and multistage fitness test (MSFT). A one-way ANOVA with Bonferroni post hoc compared between-group fitness test performance. A multiple stepwise regression calculated whether recruit characteristics or fitness could predict separation. The GRAD group was younger than the SEPAS group (p < 0.01), faster in the 75PR than the SEPFI group (p = 0.02), and completed more MSFT shuttles than the SEPPR and SEPFI groups (p = 0.01). Age predicted GRAD and SEPAS group inclusion; MSFT predicted GRAD, SEPPR, and SEPFI group inclusion. Recruits who had superior high-intensity running capacity (75PR) and aerobic fitness (MSFT) should have a better chance of completing academy. However, this could be influenced by training practices adopted during academy.

Joint moments during sprinting in unilateral transfemoral amputees wearing running-specific prostheses.

ABSTRACTKnowledge of joint moments will provide greater insight into the manner in which lower-extremity amputees wearing running-specific prostheses regain running capacity and compensate for replacement of an active leg with a passive prosthetic implement. Thus, the purpose of this study was to investigate three-dimensional joint moments during sprinting for unilateral transfemoral amputees wearing running-specific prostheses. Ten sprinters with unilateral transfemoral amputation performed maximal sprinting at the 22 m mark while wearing running-specific prostheses. Joint moments were calculated through an inverse dynamics approach. All peak flexion and extension moments in the prosthetic leg were found to be lower than those of the intact leg, except for the peak plantar flexion moment. In the frontal plane, the peak adduction and abduction moments in the prosthetic leg were generally lower than those of the intact leg. The peak internal rotation moments differed significantly between the legs, but the peak external rotation moments did not. The results of the present study suggest that asymmetric joint moment adaptations occur for unilateral transfemoral amputees to compensate for replacement of the biological leg with a passive prosthetic knee joint and running-specific prosthesis.

Skeletal muscle metabolism in rats with low and high intrinsic aerobic capacity: Effect of aging and exercise training.

PurposeExercise training increases aerobic capacity and is beneficial for health, whereas low aerobic exercise capacity is a strong independent predictor of cardiovascular disease and premature death. The purpose of the present study was to determine the metabolic profiles in a rat model of inborn low versus high capacity runners (LCR/HCR) and to determine the effect of inborn aerobic capacity, aging, and exercise training on skeletal muscle metabolic profile.MethodsLCR/HCR rats were randomized to high intensity low volume interval treadmill training twice a week or sedentary control for 3 or 11 months before they were sacrificed, at 9 and 18 months of age, respectively. Magnetic resonance spectra were acquired from soleus muscle extracts, and partial least square discriminative analysis was used to determine the differences in metabolic profile.ResultsSedentary HCR rats had 54% and 30% higher VO2max compared to sedentary LCR rats at 9 months and 18 months, respectively. In HCR, exercise increased running speed significantly, and VO2max was higher at age of 9 months, compared to sedentary counterparts. In LCR, changes were small and did not reach the level of significance. The metabolic profile was significantly different in the LCR sedentary group compared to the HCR sedentary group at the age of 9 and 18 months, with higher glutamine and glutamate levels (9 months) and lower lactate level (18 months) in HCR. Irrespective of fitness level, aging was associated with increased soleus muscle concentrations of glycerophosphocholine and glucose. Interval training did not influence metabolic profiles in LCR or HCR rats at any age.ConclusionDifferences in inborn aerobic capacity gave the most marked contrasts in metabolic profile, there were also some changes with ageing. Low volume high intensity interval training twice a week had no detectable effect on metabolic profile.

Match internal load in youth elite soccer players is period, playing position and intermittent running capacity dependent

Aims: The aims of this study were: i) to verify whether player internal load (PIL) monitored via heart rate (HR) varies with game-time and playing position; ii) whether intermittent running capacity (IRC) is related to the maintenance of within-match PIL in elite youth (U-15) soccer players. Method: Twenty-one elite soccer players (14±0.5 yrs, 172±7 cm, 63±6 kg) had their heart rate monitored (beats/min) in five matches and were tested twice for IRC (Yo-YoIR2, distance [m]) over a seven-week competitive season. Percentage of maximal heart rate (%HRmax) and time spent (TS%) in five zones (Z1[ 96%]) were our PIL indexes. Data from three complete games in the same position of each player were analyzed and matches halves, time intervals (T1 to T6), and playing positions (fullbacks, central defenders and forwards [N=5 each], midfielders [N=6]) were compared, and the relationship between IRC and within-match PIL was determined. Results: PIL was higher in 1st (86±3%) than in the 2nd half (84±4%; p<.001). The 2nd half had more TS% in Z1 and Z2 (p<.05). PIL in T4 was the lowest (p<.01), and in T6, it was lower than T1 and T2 (p<.01). Fullbacks and midfielders showed higher PIL and higher TS% in Z4 (p<.05) than the other positional roles. The average IRC correlated with PIL in T6 (r=.56, p<.01) only. Conclusion: In conclusion, the internal load in elite youth (U-15) soccer players varies with game-time and playing position; and their IRC is related to the maintenance of within-match PIL.

PO-201 Aging attenuates the effect of aerobic capacity in muscle and serum metabolic profile but not in white adipose tissue

Objective Aerobic capacity is a quantitative predictor of the morbidity and mortality in many diverse patient populations. While aging is the main factor affecting aerobic capacity. The present study aimed to assess the effect of aerobic capacity and aging on metabolic profile in rats and to investigate the metabolic interactions between white adipose tissue (WAT), muscle and serum.&#x0D; Methods In this study, we used rat models that were selectively bred to differ in maximal running capacity (High capacity runners (HCR) and Low capacity runners (LCR)). Part of the rats were sacrificed after 9 months and the rest at 21 months. The effect of aerobic capacity on metabolic profile was assessed from 9 months old young rats (HCR-Y and LCR-Y), while the effect of aging on the metabolic profile in different capacity rats was determined comparing 9 months to 21 months old rats (HCR-O and LCR-O). Nuclear magnetic resonance (NMR) spectroscopy was performed to detect the metabolomics of WAT, muscle and serum. Partial least-squares-discriminant analysis (PLS-DA) was used for pattern recognition between HCR-Y and LCR-Y and between HCR-O and LCR-O. Metabolites with variable influence on projection (VIP) &gt;1.0 and p&lt;0.05 were classified as significantly different metabolites between groups. Spearman correlation was used to assess the metabolic interactions between white adipose tissue (WAT), muscle and serum.&#x0D; Results HCR-Y rats had significantly higher skeletal muscle mass-to-body mass ratio (p&lt;0.001), while lower body mass (p&lt;0.001), fat mass (p&lt;0.001), skeletal muscle mass (p=0.035) and fat mass to body mass ratio (p=0.004) than LCR-Y rats. The running capacity of HCR-Y rats was 132.7% (best running speed) better than LCR-Y rats (p&lt;0.001). However, with age, the difference between body compositions between the two capacity groups became insignificant. HCR-O only had significantly lower body mass than the LCR-O (p=0.02). Running capacity (p=0.06) was 86.4% (best running speed) higher in the HCR-O rats than that of the LCR-O rats. PLS-DA revealed marked effects of aerobic capacity on metabolic profile in all three tissue types between HCR-Y and LCR-Y. The metabolic profile classification and prediction was best (i.e. sharper) in muscle than in WAT and serum. In addition, muscle and serum contained more significantly different metabolites than WAT in HCR-Y than in LCR-Y. Pathway analysis of the significantly different metabolites between HCR-Y and LCR-Y revealed that all the pathways belong to the lipid metabolism and amino acid metabolism in muscle while in serum it is only amino acid metabolism. However, in the case of the old groups, the PLS-DA gave reversed results. It revealed that WAT performed best in terms of classification and prediction of metabolites between HCR-O and LCR-O and had the most significantly different metabolites out of the three tissue types. The significantly different metabolites’ pathways belong to lipid metabolism in WAT. When assessing the metabolic interaction between different tissue types, all significantly different metabolites between HCR and LCR rats in young and old groups were moderately or strongly correlated (Spearman correlation between 0.45-0.9) with one or more metabolites in any of the three tissues.&#x0D; Conclusions In this study, we assessed the metabolic profile and body composition of WAT, muscle and serum in young and old rats with different aerobic capacities. We found that aerobic capacity greatly impacts body composition and the metabolic profile in muscle and serum in young rats, however the impact is attenuated with age. In addition, it is aging and not aerobic capacity that had the most influence on WAT metabolites. This suggest that WAT has more important role in aging process than previously assumed.

Influence of corticosterone on growth, home-cage activity, wheel running, and aerobic capacity in house mice selectively bred for high voluntary wheel-running behavior

Glucocorticoids, a class of metabolic hormones, impact a wide range of traits (e.g., behavior, skeletal growth, muscle maintenance, glucose metabolism), and variation in concentrations of circulating glucocorticoids (such as corticosterone), at the level of natural individual variation, in relation to endocrine disorders, or from exogenous supplementation, have manifold effects. Changes in circulating corticosterone concentrations can also impact multiple aspects of locomotor behavior, including both motivation and physical ability for exercise. To examine further the role of corticosterone in locomotor behavior and associated traits, we utilized laboratory house mice from a long-term experiment that selectively breeds for high levels of voluntary exercise. As compared with four non-selected control (C) lines, mice from the four replicate High Runner (HR) lines have ~2-fold higher baseline circulating corticosterone concentrations as well as ~3-fold higher voluntary wheel running on a daily basis, higher home-cage activity when deprived of wheels, higher maximal aerobic capacity, and smaller body size; potentially, all of these differences could be modulated by circulating corticosterone. We administered 50 μg/mL corticosterone-21-hemisuccinate in the drinking water of both HR and C male mice from weaning through ~8 weeks of age. As compared with mice from C lines, HR mice had higher endogenous corticosterone levels; higher daily wheel-running distance, duration, and speed; higher maximal oxygen consumption during forced exercise (VO2max); spent more time in the closed arms of an elevated plus maze; and had larger reproductive fat pads. For both HR and C mice, corticosterone treatment strongly suppressed endogenous circulating corticosterone levels, decreased growth rate and adult body mass, increased food and water consumption (both adjusted for body mass), increased entries into closed arms of an elevated plus maze, decreased home-cage activity (total and average intensity), decreased wheel-running distance and maximum speed, and decreased VO2max. At the suborganismal level, corticosterone treatment decreased relative adrenal, liver, and triceps surae muscle mass, as well as tail length, but increased both subdermal and reproductive fat pad masses, as well as hematocrit. Overall, the responses of both HR and C mice to corticosterone supplementation were “negative” from a health perspective. These results have significant implications for understanding both the evolution of baseline corticosterone levels and stress-related effects on activity levels. They also suggest that patients experiencing extended periods of glucocorticoid treatment might benefit from attempts to increase their physical activity as an adjuvant.

PO-002 Relationship between Air Pollution and College Students' Stamina

Objective To find out whether the air quality in the long growing areas of adolescents affects their cardiorespiratory function through experiments.&#x0D; Methods Through the classified statistics of the habitation of the students at H university，and the related statistics of the physical fitness test scores in the first and last year of college (men's 1000 meters run, the women's 800-meter run and vital capacity) and the average index of air pollution.&#x0D; Results 1.There are positive correlation between pollution index of key cities all over the country and vital capacity of freshman in the region, but after four years living under a common environment, correlation of female lung capacity level and regional air pollution index disappears, while the correlation enhances of boys. 2. Senior students’ vital capacity results are improved; 3.There is no obvious relation between the endurance performance of freshman and senior and regional pollution index. &#x0D; Conclusions 1 Air pollution and lung capacity are positively correlated, more exercise can weaken the effect of atmospheric pollution on lung. 2 After four years of urban life where the atmospheric pollution index is low, lung function can get some improvement. 3 Superimposed effects of smoking and air pollution is more severe to the lungs, last longer and less reversible .

Western-blot, PCR and immunofluorescence analysis in mitochondrial biogenesis studies

Mitochondria are providing an essential amount of energy to the cell, to achieve in homeostasis, metabolic increases, proliferation and differentiation processes. Also, mitochondrial deficiencies have severe or lethal impacts on cell viability. Among the 3000 proteins involved in mitochondrial activities, ATAD3 is a major one as essential for mitochondrial biogenesis, vital as early as embryonic implantation. In order to see its impact at animal level, we have used ATAD3+/- mice to investigate its role in running training and in high calorie diet. We found here that ATAD3 expression level avoids running capacity improvement and has a strong effect on weight increase, underlying its important role in mitochondrial mass regulations. Prior to this presentation we will emphasize on the potential of Western-blot, PCR and immunofluorescence analysis in biomedical researches.

High‐intensity interval training slows down tumor progression in mice bearing Lewis lung carcinoma

AbstractBackgroundWe aimed to determine whether a short‐term high‐intensity interval training (HIIT) protocol could counteract tumor progression in an experimental model of lung cancer.MethodsMice were injected subcutaneously with Lewis Lung Carcinoma (LLC) cells and then randomly assigned into two groups: sedentary mice (LLC group) or mice submitted to HIIT (LLC + HIIT group).ResultsLLC + HIIT group had lower tumor mass than LLC group (‐52% after 18 days), with no differences in glycolytic activity as measured by PET/CT imaging. HIIT increased Cd274 (PD‐L1) mRNA expression by ~6 folds and Vegfa mRNA expression by 2.5 folds, suggesting that HIIT stimulates local inflammation and angiogenesis in LLC tumors. Additionally, HIIT improved running capacity, skeletal muscle contractility and survival rate in LLC tumor‐bearing mice.ConclusionsThese novel findings demonstrate that a short‐term HIIT protocol slows down tumor progression, ultimately increasing survival in LLC tumor‐bearing mice. Thus, this study provides novel pre‐clinical evidence that exercise training may be a beneficial co‐therapy for lung cancer.

SEPAKBOLA DI KETINGGIAN: LITERATURE REVIEW

Abstract Soccer is often facing many various kind of situation and environmental factors, that can affects the performance of soccer players. This environmental factors can be influencing, one of them is altitude factor that can have impact to the physiology of soccer players mark by declining technical performance. This can be happen both competitive or non competitive match of soccer, researchs show a report reduction total distance cover by players (2.6-57%) when play at high intensity that can lead to hypoxia, a condition of lack oxygen at players’s body. When exercise at this circumstances, observation report greater pertubation of metabolism, plus reduction of running capacity. Fact show the different that activity with high speed and accelaration when play at 1600 m and 3600 above sea level report decrease (9-25%). And it also show the multiple effect beside decrease at speed, due to decline of partial oxygen, it also affect negative to metabolism system, because of reduction of adenosine triphosphate (ATP) at higher altitude and another system as well that lead to decrement in performance. In this review article explain altitude by collecting up to date paper information of altitude sport science and important data inside, it also inform us to know the impact factor that altitude provide to the players. That can change the way of the game and the match outcome.

Effects of Early Life Undernutrition on Maximum Treadmill Running Capacity in Mice

Undernourishment in early life has been shown to impair cardiovascular function, which could potentially influence maximum exercise capacity in adulthood. PURPOSE: To determine the effects of early life undernutrition on maximal exercise capacity in adulthood. METHODS: Using a cross fostering model, pups were undernourished either during gestation (GUN) or lactation (PUN; PN1-21) by feeding the dam a low-protein diet (8% protein) to decrease milk production. Control pups were born and suckled to dams fed an isocaloric diet with 20% protein content. At postnatal day 21 (PN21), all mice were weaned and switched to a control diet. To assess exercise capacity, mice began a 5-day treadmill acclimation protocol at PN61. At PN67, mice underwent a maximum work test, which began at 10 meters/minute with a 10% grade. Speed was increased every two minutes until exhaustion. The amount of work completed by each mouse was calculated as: Maximum Work(J)= 9.8 x Maximum Speed (m/min) x grade(radians) x Time (min) x Weight (kg). A two-way ANOVA was used to determine differences in maximal work and cardiac parameters between groups with the effects of gender and diet. RESULTS: GUN (0.3312±0.037 J) mice performed higher than PUN (0.2527±0.050 J) and CON (0.2674±0.030 J) mice on a maximum work test (p<0.05). There was no gender effect. CONCLUSION: Undernourishment during lactation leads to lower work capacity, indicating that developmental programing during the first 21 days of life impairs work capacity during adulthood.