Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1α.

Cellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and their related key proteins in response to physical activity and BCAA deprivation. By means of confocal microscopy, we examined IMCL and the lipid droplet coating proteins PLIN2 and PLIN5 in human twin pairs discordant for physical activity. Additionally, in order to study IMCLs, PLINs and their association to peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in cytosolic and nuclear pools, we mimicked exercise-induced contractions in C2C12 myotubes by electrical pulse stimulation (EPS), with or without BCAA deprivation. The life-long physically active twins displayed an increased IMCL signal in type I fibers when compared to their inactive twin pair. Moreover, the inactive twins showed a decreased association between PLIN2 and IMCL. Similarly, in the C2C12 cell line, PLIN2 dissociated from IMCL when myotubes were deprived of BCAA, especially when contracting. In addition, in myotubes, EPS led to an increase in nuclear PLIN5 signal and its associations with IMCL and PGC-1α. This study demonstrates how physical activity and BCAA availability affects IMCL and their associated proteins, providing further and novel evidence for the link between the BCAA, energy and lipid metabolisms.

Heme Oxygenase-1 and Blood Bilirubin Are Gradually Activated by Oral D-Glyceric Acid.

It has been shown that small doses of oral D-glyceric acid (DGA) activate mitochondrial metabolism and reduce inflammation among 50-60-year-old healthy volunteers. The present results with the same small doses reveal that after a 4-day DGA regimen, a dose of DGA activated the HO-1 pathway acutely, while enhanced inflammatory status after the 4-day DGA regimen seemed to be able to downregulate the HO-1 pathway in non-acute measurement. Blood bilirubin was strongly upregulated towards the end of the altogether 21-day study period with positive associations towards improved inflammation and reduced blood triglycerides. After the 4-day DGA regimen, hepatic inflow of blood bilirubin with albumin as the carrier was clearly upregulated in the lower-aerobic-capacity persons. At the same time also, blood triglycerides were down, pointing possibly to the activation of liver fatty acid oxidation. The combination of activated aerobic energy metabolism with transient HO-1 pathway activation and the upregulation of blood bilirubin may reduce the risks of chronic diseases, especially in aging. Furthermore, there exist certain diseases with unsatisfactorily-met medical needs, such as fatty and cholestatic liver diseases, and Parkinson's disease, that can be possibly ameliorated with the whole-body mechanism of the action of the DGA regimen.

Accelerometer-Based Sedentary Time, Physical Activity, and Serum Metabolome in Young Men.

Physical activity (PA) has been shown to associate with many health benefits but studies with metabolome-wide associations with PA are still lacking. Metabolome studies may deepen the mechanistic understanding of PA on the metabolic pathways related to health outcomes. The aim of the present study was to study the association of accelerometer based sedentary time (SB) and PA with metabolome measures. SB and PA were measured by a hip-worn accelerometer in 314 young adult men (age: mean 28, standard deviation 7 years). Metabolome was analyzed from fasting serum samples consisting of 66 metabolome measures (nuclear magnetic resonance-based metabolomics). The associations were analyzed using a single and compositional approach with regression analysis. The compositional analysis revealed that 4 metabolome variables were significantly (γ: 0.32−0.44, p ≤ 0.002), and 13 variables with a trend towards significance (p < 0.05), associated with SB with varying metabolic pathways. Trends towards significant associations (p < 0.05) were observed with 5 variables with moderate-to-vigorous and 1 variable with light intensity PA with varying metabolic pathways. The present study revealed possible mechanistic pathways relevant for the interaction between especially SB but also PA of moderate-to-vigorous intensity with ketone bodies and amino acid concentration related to exercised-induced energy production and lipid metabolism.

Resistance exercise with different workloads have distinct effects on cellular respiration of peripheral blood mononuclear cells.

Little is known how acute exercise-induced inflammation and metabolic stress affect immune cell bioenergetics and the portion of its components. Therefore, we investigated acute effects of eccentric-only (E), concentric-only (C) and combined eccentric-concentric resistance exercise (E + C) bouts on cellular respiration of peripheral blood mononuclear cells (PBMCs). Twelve strength-trained young men performed bench press resistance exercises in randomized order. Venous blood samples were drawn at pre-, 5 min post- and 24 h post-exercise. Several PBMC respiration states were measured using high-resolution respirometry. Levels of leukocytes, interleukin 6 (IL-6), C-reactive protein (CRP), creatine kinase (CK), blood lactate and maximum voluntary isometric force were measured from the same time points. Effects of blood lactate and pH change on bioenergetics of PBMCs were investigated ex vivo. PBMC routine respiration (p = 0.017), free routine capacity (p = 0.025) and ET-capacity (p = 0.038) decreased immediately after E + C. E responded in opposite manner 5 min post-exercise compared to E + C (p = 0.013) and C (p = 0.032) in routine respiration, and to E + C in free routine activity (p = 0.013). E + C > C > E was observed for increased lactate levels and decreased isometric force that correlated with routine respiration (R = -0.369, p = 0.035; R = 0.352, p = 0.048). Lactate and pH change did not affect bioenergetics of PBMCs. Acute resistance exercise affected cellular respiration of PBMCs, with training volume and the amount of metabolic stress appear influential. Results suggest that acute inflammation response does not contribute to changes seen in cellular respiration, but the level of peripheral muscle fatigue and metabolic stress could be explaining factors.

Branched-Chain Amino Acid Deprivation Decreases Lipid Oxidation and Lipogenesis in C2C12 Myotubes.

Impaired lipid metabolism is a common risk factor underlying several metabolic diseases such as metabolic syndrome and type 2 diabetes. Branched-chain amino acids (BCAAs) that include valine, leucine and isoleucine have been proven to share a role in lipid metabolism and hence in maintaining metabolic health. We have previously introduced a hypothesis suggesting that BCAA degradation mechanistically connects to lipid oxidation and storage in skeletal muscle. To test our hypothesis, the present study examined the effects of BCAA deprivation and supplementation on lipid oxidation, lipogenesis and lipid droplet characteristics in murine C2C12 myotubes. In addition, the role of myotube contractions on cell metabolism was studied by utilizing in vitro skeletal-muscle-specific exercise-like electrical pulse stimulation (EPS). Our results showed that the deprivation of BCAAs decreased both lipid oxidation and lipogenesis in C2C12 myotubes. BCAA deprivation further diminished the number of lipid droplets in the EPS-treated myotubes. EPS decreased lipid oxidation especially when combined with high BCAA supplementation. Similar to BCAA deprivation, high BCAA supplementation also decreased lipid oxidation. The present results highlight the role of an adequate level of BCAAs in healthy lipid metabolism.

Enlarged PLIN5-uncoated lipid droplets in inner regions of skeletal muscle type II fibers associate with type 2 diabetes.

Skeletal muscle physiology remains of paramount importance in understanding insulin resistance. Due to its high lipid turnover rates, regulation of intramyocellular lipid droplets (LDs) is a key factor. Perilipin 5 (PLIN5) is one of the most critical agents in such regulation, being often referred as a protector against lipotoxicity and consequent skeletal muscle insulin resistance. We examined area fraction, size, subcellular localization and PLIN5 association of LDs in two fiber types of type 2 diabetic (T2D), obese (OB) and healthy (HC) individuals by means of fluorescence microscopy and image analysis. We found that T2D type II fibers have a significant sub-population of large and internalized LDs, uncoated by PLIN5. Based on this novel result, additional hypotheses for the pathophysiology of skeletal muscle insulin resistance are formulated, together with future research directions.

Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus.

BACKGROUND: Increasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats. METHODS: We examined markers for inflammation and brain plasticity in the hippocampi of LCR rats and compared them to HCR rats. The effect of age was determined by studying the rats at a young age (8 weeks) and later in life (40 weeks). We used western blots and immunohistochemistry to quantify the expression of target proteins. RESULTS: Our study showed that the number of adult-born new neurons in the hippocampus was significantly lower in LCR rats than it was in HCR rats already at a young age and that the difference became more pronounced with age. The expression of synaptic proteins was higher in young animals relative to older ones. Brain inflammation tended to be higher in LCR rats than it was in the HCR rats, and more prominent in older rats than in young ones. CONCLUSION: Our study is the first to demonstrate that low intrinsic aerobic fitness that is associated with obesity and poor metabolic health is also linked with reduced hippocampal structural plasticity at a young age. Our results also suggest that inflammation of the brain could be one factor mediating the link between obesity and poor cognitive performance.

Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation.

The application of exercise-like electrical pulse simulation (EL-EPS) has become a widely used exercise mimetic in vitro. EL-EPS produces similar physiological responses as in vivo exercise, while less is known about the detailed metabolic effects. Routinely, the C2C12 myotubes are cultured in high-glucose medium (4.5 g/L), which may alter EL-EPS responses. In this study, we evaluate the metabolic effects of EL-EPS under the high- and low-glucose (1.0 g/L) conditions to understand how substrate availability affects the myotube response to EL-EPS. The C2C12 myotube, media, and cell-free media metabolites were analyzed using untargeted nuclear magnetic resonance (NMR)-based metabolomics. Furthermore, translational and metabolic changes and possible exerkine effects were analyzed. EL-EPS enhanced substrate utilization as well as production and secretion of lactate, acetate, 3-hydroxybutyrate, and branched-chain fatty acids (BCFAs). The increase in BCFAs correlated with branched-chain amino acids (BCAAs) and BCFAs were strongly decreased when myotubes were cultured without BCAAs suggesting the action of acyl-CoA thioesterases on BCAA catabolites. Notably, not all EL-EPS responses were augmented by high glucose because EL-EPS increased phosphorylated c-Jun N-terminal kinase and interleukin-6 secretion independent of glucose availability. Administration of acetate and EL-EPS conditioned media on HepG2 hepatocytes had no adverse effects on lipolysis or triacylglycerol content. Our results demonstrate that unlike in cell-free media, the C2C12 myotube and media metabolites were affected by EL-EPS, particularly under high-glucose condition suggesting that media composition should be considered in future EL-EPS studies. Furthermore, acetate and BCFAs were identified as putative exerkines warranting more research.NEW & NOTEWORTHY The present study examined for the first time the metabolome of 1) C2C12 myotubes, 2) their growth media, and 3) cell-free media after exercise-like electrical pulse stimulation under distinct nutritional loads. We report that myotubes grown under high-glucose conditions had greater responsiveness to EL-EPS when compared with lower glucose availability conditions and increased media content of acetate and branched-chain fatty acids suggests they might act as putative exerkines warranting further research.

Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue.

Aerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging, and their interaction on metabolism, we utilized rat models selectively bred for low and high intrinsic aerobic capacity (LCRs/HCRs) and compared the metabolomics of serum, muscle, and white adipose tissue (WAT) at two time points: Young rats were sacrificed at 9 months of age, and old rats were sacrificed at 21 months of age. Targeted and semi-quantitative metabolomics analysis was performed on the ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS) platform. The effects of aerobic capacity, aging, and their interaction were studied via regression analysis. Our results showed that high aerobic capacity is associated with an accumulation of isovalerylcarnitine in muscle and serum at rest, which is likely due to more efficient leucine catabolism in muscle. With aging, several amino acids were downregulated in muscle, indicating more efficient amino acid metabolism, whereas in WAT less efficient amino acid metabolism and decreased mitochondrial ß-oxidation were observed. Our results further revealed that high aerobic capacity and aging interactively affect lipid metabolism in muscle and WAT, possibly combating unfavorable aging-related changes in whole body metabolism. Our results highlight the significant role of WAT metabolism for healthy aging.

A collagen extraction and deuterium oxide stable isotope tracer method for the quantification of bone collagen synthesis rates in vivo.

The development of safe and practical strategies to prevent weakening of bone tissue is vital, yet attempts to achieve this have been hindered by a lack of understanding of the short-term (days-weeks) physiology of bone collagen turnover. To address this, we have developed a method to quantify bone collagen synthesis in vivo, using deuterium oxide (D2 O) tracer incorporation techniques combined with gas chromatography pyrolysis isotope-ratio mass spectrometry (GC-pyrolysis-IRMS). Forty-six male and female rats from a selectively bred model ingested D2 O for 3 weeks. Femur diaphyses (FEM), tibia proximal (T-PRO), and distal (T-DIS) epiphyses-metaphyses and tibia mid-shaft diaphyses (T-MID) were obtained from all rats after necropsy. After demineralisation, collagen proteins were isolated and hydrolysed and collagen fractional synthetic rates (FSRs) determined by incorporation of deuterium into protein-bound alanine via GC-pyrolysis-IRMS. The collagen FSR for the FEM (0.131 ± 0.078%/day; 95% CI [0.106-0.156]) was greater than the FSR at T-MID (0.055 ± 0.049%/day; 95% CI [0.040-0.070]; p < 0.001). The T-PRO site had the highest FSR (0.203 ± 0.123%/day; 95% CI [0.166-0.241]) and T-DIS the lowest (0.027 ± 0.015%/day; 95% CI [0.022-0.031]). The three tibial sites exhibited different FSRs (p < 0.001). Herein, we have developed a sensitive method to quantify in vivo bone collagen synthesis and identified site-specific rates of synthesis, which could be applicable to studies of human bone collagen turnover.

Rats with elevated genetic risk for metabolic syndrome exhibit cognitive deficiencies when young.

Metabolic syndrome (MetS) is a known risk factor for cognitive decline. Using polygenic rat models selectively bred for high and low intrinsic exercise capacity and simultaneously modelling as low and high innate risk factor for MetS respectively, we have previously shown that adult animals with lower exercise capacity/higher MetS risk perform poorly in tasks requiring flexible cognition. However, it is not known whether these deficits in cognition are present already at young age. Also, it is unclear whether the high risk genome is related also to lower-level cognition, such as sensory gating measured as prepulse inhibition. In this study, young and adult (5-8 weeks and ~9 months) rats selectively bred for 36 generations as High-Capacity Runners (HCR) or Low-Capacity Runners (LCR) were tested for behavior in an open field task, modulation of startle reflex, and spatial learning in a T-maze. HCR rats were more active in the open field than LCR rats independent of age. Responses to the startle stimulus habituated to the same extent in LCR compared to HCR rats when young, but as adults, stronger habituation was seen in the HCR animals. The prepulse inhibition of startle response was equally strong in young HCR and LCR animals but the effect was shorter lasting in HCR animals. In T-maze, adult HCR animals unexpectedly showed attenuated learning, but we interpret this finding to stem from differences in motivation rather than learning ability. Overall, in the LCR rats with the risk genome for poor aerobic fitness and MetS, indications of compromised cognitive function are present already at a young age.

Randomized Trial: D-Glyceric Acid Activates Mitochondrial Metabolism in 50-60-Year-Old Healthy Humans.

Background: Based on earlier studies, natural metabolite D-glyceric acid (DGA) does not seem to play any role in whole-body metabolism. Nevertheless, one ethanol oxidation-related rat study with controversial results raised our interest. According to preparatory studies for the regulatory approval of DGA, some highly conserved mechanism seems to subtly activate the cellular energy metabolism. Therefore, the present 25-days double-blind human study with placebo control was initiated. Purpose: The main target in the present study with 27 healthy 50-60-year-old human volunteers was to find out whether an "acute" 4-days and a longer 21-days exogenous DGA regimen caused moderate activation of the mitochondrial energy metabolism. The simultaneous target was to find out whether a halved dose of DGA continued to be an effective regimen. Main Findings: The results revealed the following statistically significant findings: 1) plasma concentrations of metabolites related to aerobic energy production, especially lactate, were strongly reduced, 2) systemic inflammation was lowered both in 4- and 21-days, 3) mitochondria-related mRNA expressions in circulating immune cells were noticeably modulated at Day4, 4) cellular membrane integrity seemed to be sharply enhanced, and 5) cellular NADH/NAD+ -ratio was upregulated. Conclusion: Mitochondrial metabolism was clearly upregulated at the whole-body level in both 4- and 21 days. At the same time, the effect of DGA was very well tolerated. Based on received solid results, the DGA regimen may alleviate acute and chronic energy metabolic challenges in main organs like the liver, CNS, and skeletal muscles. Enhanced membrane integrity combined with lower systemic inflammation and activated metabolic flows by the DGA regimen may be beneficial especially for the aging population.

Effects of aerobic and strength training on aerobic capacity, muscle strength, and gene expression of lymphomonocytes in patients with stable CAD.

This study examined the effectiveness, suitability, and safety of a mixed interval-type aerobic and strength training program (MIAST) on physical fitness in patients with stable coronary artery disease (CAD) without history of myocardial infarction (MI). Twenty-three patients with stable CAD were randomly assigned to a MIAST (n = 12; mean age 58.6 years) or control (n = 11; 63.3 years) group. The MIAST group participated in the progressive training program twice a week for 21 weeks. Peak oxygen uptake (VO2peak), workload, and exercise time were measured as were maximal muscle strength, serum lipids, glucose concentration, and the cross-sectional area (CSA) of knee extensors. The safety and suitability of the program were assessed by wireless electrocardiogram (ECG) monitoring and exercise diaries. VO2peak (6.9%; P < 0.05) and exercise time (11.2%; P < 0.05) improved significantly after 12 weeks of training in the MIAST group compared to the control group. Muscle strength (19.9%; P < 0.05) and CSA (2.2%; P < 0.05) increased, and serum lipids and blood glucose tended to decrease after the training. The successful training program (increase in maximal oxygen uptake) increased the gene expression of oxygen metabolism and decreased the gene expression of inflammation pathways in lymphomonocytes. The MIAST program, including interval-type aerobic and strength training, was safe, did not cause any adverse effects, and led to significant improvements in physical fitness in patients with stable CAD.

Striated muscle-specific serine/threonine-protein kinase beta segregates with high versus low responsiveness to endurance exercise training.

Bidirectional selection for either high or low responsiveness to endurance running has created divergent rat phenotypes of high-response trainers (HRT) and low-response trainers (LRT). We conducted proteome profiling of HRT and LRT gastrocnemius of 10 female rats (body weight 279 ± 35 g; n = 5 LRT and n = 5 HRT) from generation 8 of selection. Differential analysis of soluble proteins from gastrocnemius was conducted by label-free quantitation. Genetic association studies were conducted in 384 Russian international-level athletes (age 23.8 ± 3.4 yr; 202 men and 182 women) stratified to endurance or power disciplines. Proteomic analysis encompassed 1,024 proteins, 76 of which exhibited statistically significant (P < 0.05, false discovery rate <1%) differences between HRT and LRT muscle. There was significant enrichment of enzymes involved in glycolysis/gluconeogenesis in LRT muscle but no enrichment of gene ontology phrases in HRT muscle. Striated muscle-specific serine/threonine-protein kinase-beta (SPEG-ß) exhibited the greatest difference in abundance and was 2.64-fold greater (P = 0.0014) in HRT muscle. Coimmunoprecipitation identified 24 potential binding partners of SPEG-ß in HRT muscle. The frequency of the G variant of the rs7564856 polymorphism that increases SPEG gene expression was significantly greater (32.9 vs. 23.8%; OR = 1.6, P = 0.009) in international-level endurance athletes (n = 258) compared with power athletes (n = 126) and was significantly associated (ß = 8.345, P = 0.0048) with a greater proportion of slow-twitch fibers in vastus lateralis of female endurance athletes. Coimmunoprecipitation of SPEG-ß in HRT muscle discovered putative interacting proteins that link with previously reported differences in transforming growth factor-ß signaling in exercised muscle.

Fat oxidation at rest and during exercise in male monozygotic twins.

PURPOSE: We aimed to investigate if hereditary factors, leisure-time physical activity (LTPA) and metabolic health interact with resting fat oxidation (RFO) and peak fat oxidation (PFO) during ergometer cycling. METHODS: We recruited 23 male monozygotic twin pairs (aged 32-37 years) and determined their RFO and PFO with indirect calorimetry for 21 and 19 twin pairs and for 43 and 41 twin individuals, respectively. Using physical activity interviews and the Baecke questionnaire, we identified 10 twin pairs as LTPA discordant for the past 3 years. Of the twin pairs, 8 pairs participated in both RFO and PFO measurements, and 2 pairs participated in either of the measurements. We quantified the participants' metabolic health with a 2-h oral glucose tolerance test. RESULTS: Fat oxidation within co-twins was correlated at rest [intraclass correlation coefficient (ICC) = 0.54, 95% confidence interval (CI) 0.15-0.78] and during exercise (ICC = 0.67, 95% CI 0.33-0.86). The LTPA-discordant pairs had no pairwise differences in RFO or PFO. In the twin individual-based analysis, PFO was positively correlated with the past 12-month LTPA (r = 0.26, p = 0.034) and the Baecke score (r = 0.40, p = 0.022) and negatively correlated with the area under the curve of insulin (r = - 0.42, p = 0.015) and glucose (r = - 0.31, p = 0.050) during the oral glucose tolerance test. CONCLUSIONS: Hereditary factors were more important than LTPA for determining fat oxidation at rest and during exercise. Additionally, PFO, but not RFO, was associated with better metabolic health.

Associations of Aerobic Fitness and Maximal Muscular Strength With Metabolites in Young Men.

Importance: High physical fitness is associated with a reduction in risk of cardiovascular diseases and death, but the underlying mechanisms are insufficiently understood. Objective: To determine how aerobic fitness and muscular strength are associated with serum metabolome measures. Design, Setting, and Participants: This cross-sectional study included Finnish men receiving military refresher training from May 5, 2015, to November 28, 2015, representing partly overlapping groups of individuals with the lowest vs highest aerobic fitness and the lowest vs highest muscular strength. Data analyses were conducted from January 1, 2018, to May 31, 2019. Main Outcomes and Measures: The associations of aerobic fitness (determined with maximum oxygen consumption in milliliters per minute per kilogram, measured with maximal cycle ergometer test) and muscular strength (determined with a maximal strength test for lower extremities in kilograms) with 66 metabolome measures from fasting serum samples (nuclear magnetic resonance-based metabolomics) were analyzed. Results: Participants included 580 Finnish men (mean [SD] age, 26.1 [6.5] years). Including overlap between groups, there were 196 men in the lowest aerobic fitness group and 197 men in the highest aerobic fitness group as well as 196 men in the lowest muscular strength group and 197 men in the highest muscular strength group. Of 66 studied metabolome measures, 48 differed between high vs low aerobic fitness groups, including small very low-density lipoprotein (standardized median difference, -0.67; 95% CI, -0.83 to -0.49), large high-density lipoprotein (standardized median difference, 0.89; 95% CI, 0.69-1.15), total triglyceride levels (standardized median difference, -0.52; 95% CI, -0.65 to -0.34), isoleucine (standardized median difference, -0.37; 95% CI, -0.55 to -0.16), leucine (standardized median difference, -0.55; 95% CI, -0.72 to -0.34), phenylalanine (standardized median difference, -0.54; 95% CI, -0.71 to -0.32), glycerol (standardized median difference, -0.64; 95% CI, -0.81 to -0.48), and glycoprotein (standardized median difference, -0.78; 95% CI, -0.95 to -0.62) concentration, a high unsaturation degree of fatty acids (standardized median difference, 0.59; 95% CI, 0.42-0.81), and apolipoprotein B to apolipoprotein A1 ratio (standardized median difference, -0.88; 95% CI, -1.08 to -0.67). Adding aerobic fitness into the regression model after age, education, smoking, use of alcohol, and dietary factors accounted for more than an additional 5% of variation for 25 metabolome measures (R2 range, 5.01%-15.90% by measure). With these 2 criteria, maximal muscular strength was not associated with any metabolome measures. Aerobic fitness was associated with high large high-density lipoprotein particle concentration (R2, 14.97%; 95% CI, 10.65%-20.85%), low apolipoprotein B to apolipoprotein A1 ratio (R2, 14.49%; 95% CI, 10.58%-19.51%), and low glycoprotein concentration (R2, 15.90%; 95% CI, 11.22%-21.51%). Aerobic fitness was also associated with low very low-density lipoprotein, triglyceride, isoleucine, leucine, phenylalanine, glycerol, and glycoprotein concentrations and with a high unsaturation degree of fatty acids. Adjusting for recent physical activity influenced the results minimally. Adjusting for body fat percentage showed that some of the associations were mechanistically associated with body fat percentage. Conclusions and Relevance: This study provides data on the association of high aerobic fitness with underlying oxidative lipid metabolism associated with a reduction in cardiometabolic risk. High maximal muscular strength is not similarly associated with these benefits.

Strength Training Improves Metabolic Health Markers in Older Individual Regardless of Training Frequency.

The main purpose of the present study was to investigate the effect of frequency, thereby increasing training volume, of resistance training on body composition, inflammation markers, lipid and glycemic profile in healthy older individuals (age range 65-75 year). Ninety-two healthy participants were randomly assigned to one of four groups; performing strength training one- (EX1), two- (EX2), or three- (EX3) times-per-week and a non-training control (CON) group. Whole-body strength training was performed using 2-5 sets and 4-12 repetitions per exercise and 7-9 exercises per session. All training groups attended supervised resistance training for 6 months. Body composition was measured by dual X-ray absorptiometry and fasting blood samples were taken pre- and post-training. There were significant main effects of time for total fat mass (F = 28.12, P < 0.001) and abdominal fat mass (F = 20.72, P < 0.001). Pre- to post-study, statistically significant reductions in fat mass (Δ = -1.3 ± 1.4 kg, P < 0.001, n = 26) were observed in EX3. Pre- to post-study reductions in low density lipoprotein (LDL) concentration (Δ = -0.38 ± 0.44 mmol⋅L-1, P = 0.003, n = 19) were observed only in EX3, whereas a significant pre- to post-study increases in high density lipoprotein (HDL) concentration (0.14-0.19 mmol⋅L-1) were observed in all training groups. Most variables at baseline demonstrated a significant (negative) relationship when correlating baseline values with their change during the study including: Interleukin-6 (IL-6) (r = -0.583, P < 0.001), high-sensitivity c-reactive protein (hs-CRP) (r = -0.471, P < 0.001, and systolic blood pressure (r = -0.402, P = 0.003). The present study suggests that having more than two resistance training sessions in a week could be of benefit in the management of body composition and lipid profile. Nevertheless, interestingly, and importantly, those individuals with a higher baseline in systolic blood pressure, IL-6 and hs-CRP derived greatest benefit from the resistance training intervention, regardless of how many times-a-week they trained. Finally, the present study found no evidence that higher training frequency would induce greater benefit regarding inflammation markers or glycemic profile in healthy older adults.

Physiological adaptations to resistance training in rats selectively bred for low and high response to aerobic exercise training.

NEW FINDINGS: What is the central question of this study? Can phenotypic traits associated with low response to one mode of training be extrapolated to other exercise-inducible phenotypes? The present study investigated whether rats that are low responders to endurance training are also low responders to resistance training. What is the main finding and its importance? After resistance training, rats that are high responders to aerobic exercise training improved more in maximal strength compared with low-responder rats. However, the greater gain in strength in high-responder rats was not accompanied by muscle hypertrophy, suggesting that the responses observed could be mainly neural in origin. ABSTRACT: The purpose of this study was to determine whether rats selectively bred for low and high response to aerobic exercise training co-segregate for differences in muscle adaptations to ladder-climbing resistance training. Five high-responder (HRT) and five low-responder (LRT) rats completed the resistance training, while six HRT and six LRT rats served as sedentary control animals. Before and after the 6 week intervention, body composition was determined by dual energy X-ray absorptiometry. Before tissue harvesting, the right triceps surae muscles were loaded by electrical stimulation. Muscle fibre cross-sectional areas, nuclei per cell, phosphorylation status of selected signalling proteins of mTOR and Smad pathways, and muscle protein, DNA and RNA concentrations were determined for the right gastrocnemius muscle. The daily protein synthesis rate was determined by the deuterium oxide method from the left quadriceps femoris muscle. Tissue weights of fore- and hindlimb muscles were measured. In response to resistance training, maximal carrying capacity was greater in HRT (∼3.3 times body mass) than LRT (∼2.5 times body mass), indicating greater improvements of strength in HRT. However, muscle hypertrophy that could be related to greater strength gains in HRT was not observed. Furthermore, noteworthy changes within the experimental groups or differences between groups were not observed in the present measures. The lack of hypertrophic muscular adaptations despite considerable increases in muscular strength suggest that adaptations to the present ladder-climbing training in HRT and LRT rats were largely induced by neural adaptations.

Corrected whole blood biomarkers - the equation of Dill and Costill revisited.

An exercise bout or a dehydration often causes a reduction in plasma volume, which should be acknowledged when considering the change in biomarkers before and after the plasma changing event. The classic equation from Dill and Costill (1974, J. Appl. Physiol., 37, 247-248) for plasma volume shift is usually utilized in such a case. Although this works well with plasma and serum biomarkers, we argue in this note that this traditional approach gives misleading results in the context of whole blood biomarkers, such as lactate, white cells, and thrombocytes. In this study, we demonstrate that to calculate the change in the total amount of circulating whole blood biomarker, one should utilize a formula [Formula: see text] Here Hb and BM are, respectively, the concentrations for the hemoglobin and for the inspected whole blood biomarker before (pre) and after (post) the plasma changing incident.

Enterobacter cloacae administration induces hepatic damage and subcutaneous fat accumulation in high-fat diet fed mice.

Accumulating evidence indicates that gut microbiota plays a significant role in obesity, insulin resistance and associated liver disorders. Family Enterobacteriaceae and especially Enterobacter cloacae strain B29 have been previously linked to obesity and hepatic damage. The underlying mechanisms, however, remain unclear. Therefore, we comprehensively examined the effects of E. cloacae subsp. cloacae (ATCC® 13047™) administration on host metabolism of mice fed with high-fat diet (HFD). C57BL/6N mice were randomly divided into HFD control, chow control, and E. cloacae treatment groups. The E. cloacae treatment group received live bacterial cells in PBS intragastrically twice a week, every other week for 13 weeks. Both control groups received PBS intragastrically. After the 13-week treatment period, the mice were sacrificed for gene and protein expression and functional analyses. Our results show that E. cloacae administration increased subcutaneous fat mass and the relative proportion of hypertrophic adipocytes. Both subcutaneous and visceral fat had signs of decreased insulin signaling and elevated lipolysis that was reflected in higher serum glycerol levels. In addition, E. cloacae -treated mice had significantly higher hepatic AST and AST/ALT ratio, and their liver histology indicated fibrosis, demonstrating that E. cloacae subsp. cloacae administration promotes hepatic damage in HFD fed mice.