Vertical ground reaction force measurements and video measurements provide comparable estimates of distance moved by mice during artificial light and dark periods.

Video-based measures of spontaneous activity of rodents are of interest in studying, e.g. physiology. However, video-based tracking methods typically require light. The purpose of the present study was to develop a video based method for tracking movements of mice during a dark period. The method was applied in comparing the dark and light period activities of mice. Ten male mice were used in the present study. The activity of the animals was monitored simultaneously with video and ground reaction force (GRF) recordings during consecutive 12h periods of artificial light and dark. Texture based background subtraction method was used to track the mouse from the video recording, while the weig…

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 contract…

Gluten affects epithelial differentiation-associated genes in small intestinal mucosa of coeliac patients

Summary In coeliac disease gluten induces an immunological reaction in genetically susceptible patients, and influences on epithelial cell proliferation and differentiation in the small-bowel mucosa. Our aim was to find novel genes which operate similarly in epithelial proliferation and differentiation in an epithelial cell differentiation model and in coeliac disease patient small-bowel mucosal biopsy samples. The combination of cDNA microarray data originating from a three-dimensional T84 epithelial cell differentiation model and small-bowel mucosal biopsy samples from untreated and treated coeliac disease patients and healthy controls resulted in 30 genes whose mRNA expression was simila…

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

Aim Sirtuins are proteins that connect energy metabolism, oxidative stress and aging. Expression of heat shock proteins (Hsps) is regulated by heat shock factors (HSFs) in response to various environmental and physiological stresses, such as oxidative stress. Oxidative stress accumulates during aging which makes cells more prone to DNA damage. Although many experimental animal models have been designed to study the effects of knockdown or overexpression of sirtuins, HSFs and Hsps, little is known about how aging per se affects their expression. Here we study the impact of intrinsic aerobic capacity, aging and voluntary exercise on the levels of sirtuins, HSFs and Hsps in skeletal muscle. Me…

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), crea…

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 …

Validation of a method to measure total spontaneous physical activity of sedentary and voluntary running mice

Running wheels are commonly used to stimulate physical activity of mice. To control the effects of physical activity on study results, it is important to measure the total activity (all movements) of both sedentary and running wheel stimulated mice.Because there was a lack of a validated system, we built a force-plate based system specifically for this purpose. The validity of the system and its variables (activity index, activity time and distance) were tested in calibration measurements and in situ by measuring the activity of eight mice both with and without running wheels. Four mice served as sedentary controls. Activity index adds changes in vertical reaction forces induced by moving m…

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…

Voluntary Running Aids to Maintain High Body Temperature in Rats Bred for High Aerobic Capacity

The production of heat, i.e., thermogenesis, is a significant component of the metabolic rate, which in turn affects weight gain and health. Thermogenesis is linked to physical activity (PA) level. However, it is not known whether intrinsic exercise capacity, aging, and long-term voluntary running affect core body temperature. Here we use rat models selectively bred to differ in maximal treadmill endurance running capacity (Low capacity runners, LCR and High capacity Runners, HCR), that as adults are divergent for aerobic exercise capacity, aging, and metabolic disease risk to study the connection between PA and body temperature. Ten high capacity runner (HCR) and ten low capacity runner (L…

Selective breeding for endurance running capacity affects cognitive but not motor learning in rats

The ability to utilize oxygen has been shown to affect a wide variety of physiological factors often considered beneficial for survival. As the ability to learn can be seen as one of the core factors of survival in mammals, we studied whether selective breeding for endurance running, an indication of aerobic capacity, also has an effect on learning. Rats selectively bred over 23 generations for their ability to perform forced treadmill running were trained in an appetitively motivated discrimination-reversal classical conditioning task, an alternating T-maze task followed by a rule change (from a shift-win to stay-win rule) and motor learning task. In the discrimination-reversal and T-maze …

Endurance training decreases the alkaline proteolytic activity in mouse skeletal muscles.

Alkaline and myofibrillar protease activities of rectus femoris, soleus, and tibialis anterior muscles and the pooled sample of gastrocnemius and plantaris muscles were analyzed in male NMRI-mice during a running-training program of 3, 10, or 20 daily 1-h sessions. The activity of citrate synthase increased during the endurance training, reflecting the increased oxidative capacity of skeletal muscles. The activities of alkaline and myofibrillar proteases continually decreased in the course of the training program in all muscles studied. Instead, the activity of beta-glucuronidase (a marker of lysosomal hydrolases) increased in all muscles. The highest activities were observed at the beginni…

Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice

Duchenne Muscular Dystrophy is characterized by muscle wasting and decreased aerobic metabolism. Exercise and blocking of myostatin/activin signaling may independently or combined counteract muscle wasting and dystrophies. The effects of myostatin/activin blocking using soluble activin receptor-Fc (sActRIIB-Fc) administration and wheel running were tested alone or in combination for seven weeks in dystrophic mdx mice. Expression microarray analysis revealed decreased aerobic metabolism in the gastrocnemius muscle of mdx mice compared to healthy mice. This was not due to reduced home-cage physical activity, and was further downregulated upon sActRIIB-Fc treatment in enlarged muscles. However…

Muscle inactivity is adversely associated with biomarkers in physically active adults.

PURPOSE While the lack of muscular activity is a proposed trigger for metabolic alterations, this association has not been directly measured. We examined the associations between EMG-derived muscle inactivity and activity patterns and cardiometabolic biomarkers in healthy, physically active adults. METHODS Data for this cross-sectional study were pooled from two studies (EMG24 and InPact), resulting in a sample of 150 individuals without known chronic diseases and with high-quality EMG data (female n = 85, male n = 65, age = 38.8 ± 10.6 yr, body mass index = 23.8 ± 3.1 kg·m⁻²). EMG was measured during one to three typical weekdays using EMG shorts, measuring quadriceps and hamstring muscle …

Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men.

Aims/hypothesis: Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances. Methods: Older Finnish men enriched with individuals having been athletes in y…

Label-free profiling of skeletal muscle using high-definition mass spectrometry

We report automated and time efficient (2 h per sample) profiling of muscle using ultra-performance liquid chromatography (LC) coupled directly with high-definition mass spectrometry (HDMSE). Soluble proteins extracted from rat gastrocnemius (n=10) were digested with trypsin and analysed in duplicate using a 90 min RPLC gradient. Protein identification and label-free quantitation were performed from HDMSE spectra analysed using TransOmics Informatics for Proteomics software. In total 1,514 proteins were identified. Of these, 811 had at least 3 unique peptides and were subsequently used to assess the dynamic range and precision of LC-HDMSE label-free profiling. Proteins analysed by LC-HDMSE …

Effects of fatiguing jumping exercise on mRNA expression of titin-complex proteins and calpains.

Eccentric exercise induced by electrostimulation increases mRNA expression of titin-complex proteins in rodent skeletal muscle. In this study, mRNA expression of titin, muscle LIM protein (MLP), cardiac ankyrin repeat protein (CARP), ankyrin repeat domain protein 2 (Ankrd2), diabetes-related ankyrin repeat protein (DARP), and calcium-activated proteinases, calpains, were investigated in human skeletal muscle after fatiguing jumping exercise. Fatiguing jumping exercise did not change mRNA expression of titin, DARP, calpain 1, or calpain 3. MLP, Ankrd2 and calpain 2 mRNA levels were increased 2 days postexercise. CARP mRNA level was already elevated 30 min and remained elevated 2 days postexe…

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

ABSTRACTAerobic 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 of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS)…

Are skeletal muscle FNDC5 expression and irisin release regulated by exercise and related to health?

Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n= 17), (2) a heavy-intensity resistance exercise (RE) bout (young n= 10, older n= 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n= 9), or (4) …

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 …

Effects of diet-induced obesity and voluntary wheel running on the axial and peripheral skeleton microstructure in mice

Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change

Abstract Objective The relation between lipid accumulation and influence of exercise on insulin sensitivity is not straightforward. A proper balance between lipid droplet synthesis, lipolysis, and oxidative metabolism would ensure low local intramyocellular fatty acid levels, thereby possibly protecting against lipotoxicity-associated insulin resistance. This study investigated whether the accumulation of triglycerides and lipid droplets in response to high availability of fatty acids after high-fat feeding would parallel the abundance of intramyocellular perilipin proteins, especially PLIN5. The effects on these variables after diet change or voluntary running exercise intervention in skel…

Redistribution of glucose uptake by chronic exercise, measured in isolated perfused rat hearts.

The effects of 8-9 weeks of running and swimming training on the transmural distribution of cardiac glucose uptake and protein synthesis in isolated perfused heart were studied in male rats. The left ventricular glucose uptake in hearts from sedentary rats was 2.5 +/- 0.3 mumoles/min per g protein (mean +/- S.D.), and about 30% higher in the subendocardial layer than in the subepicardial layer (P less than 0.01). After the running and swimming programs the total left ventricular glucose uptake was at the level of sedentary rats, but the gradient was absent. The rate of protein synthesis was evenly distributed through the left ventricular wall and similar in all experimental groups. The alte…

Rats bred for low aerobic capacity become promptly fatigued and have slow metabolic recovery after stimulated, maximal muscle contractions.

AIM. Muscular fatigue is a complex phenomenon affected by muscle fiber type and several metabolic and ionic changes within myocytes. Mitochondria are the main determinants of muscle oxidative capacity which is also one determinant of muscle fatigability. By measuring the concentrations of intracellular stores of high-energy phosphates it is possible to estimate the energy production efficiency and metabolic recovery of the muscle. Low intrinsic aerobic capacity is known to be associated with reduced mitochondrial function. Whether low intrinsic aerobic capacity also results in slower metabolic recovery of skeletal muscle is not known. Here we studied the influence of intrinsic aerobic capac…

A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle

Current methods to quantify in vivo RNA dynamics are limited. Here, we developed a novel stable isotope (D2O) methodology to quantify RNA synthesis (i.e., ribosomal biogenesis) in cells, animal models, and humans. First, proliferating C2C12 cells were incubated in D2O-enriched media and myotubes ±50 ng/ml IGF-I. Second, rat quadriceps (untrained, n = 9; 7-wk interval-“like” training, n = 13) were collected after ~3-wk D2O (70 atom %) administration, with body-water enrichment monitored via blood sampling. Finally, 10 (23 ± 1 yr) men consumed 150-ml D2O followed by 50 ml/wk and undertook 6-wk resistance exercise (6 × 8 repetitions, 75% 1-repetition maximum 3/wk) with body-water enrichment mo…

Effects of endurance training on alkaline protease activities in rat skeletal muscles.

This study aimed at comparing the effects of running and swimming training protocols and the termination of training on the activities of two proteases with alkaline pH-optima (alkaline protease and myofibrillar protease) in the tibialis anterior, soleus, and gastrocnemius muscles of male rats. The training on treadmill decreased the activities of alkaline and myofibrillar proteases by approx. 10-20% in the muscles studied. The activities of both proteases were unchanged in swimming-trained rats. Two weeks after the termination of running training the activity of alkaline protease was increased in gastrocnemius muscle but not in the other muscles. Swimming training increased the activity of…

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy

Background: Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. Methods: Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks. Results: Treatment of mdx mice with ActRIIB-Fc resulted in significantly…

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 ot…

PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise

The primary aim of the present study was to investigate the acute gene expression responses of PGC-1 isoforms and PGC-1a target genes related to mitochondrial biogenesis (cytochrome C), angiogenesis (VEGF-A), and muscle hypertrophy (myostatin), after a resistance or endurance exercise bout. In addition, the study aimed to elucidate whether the expression changes of studied transcripts were linked to phosphorylation of AMPK and MAPK p38. Nineteen physically active men were divided into resistance exercise (RE, n = 11) and endurance exercise (EE, n = 8) groups. RE group performed leg press exercise (10 9 10 RM, 50 min) and EE walked on a treadmill (~80% HRmax, 50 min). Muscle biopsies were ob…

Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained

Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high-intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these l…

Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle.

Diabetes alters microvascular structure and function and is a major risk factor for cardiovascular diseases. In diabetic skeletal muscle, impaired angiogenesis and reduced VEGF-A expression have been observed, whereas in healthy muscle exercise is known to have opposite effects. We studied the effects of type 1 diabetes and combined exercise training on angiogenic mRNA expression and capillarization in mouse skeletal muscle. Microarray and real-time PCR analyses showed that diabetes altered the expression of several genes involved in angiogenesis. For example, levels of proangiogenic VEGF-A, VEGF-B, neuropilin-1, VEGFR-1, and VEGFR-2 were reduced and the levels of antiangiogenic thrombospon…

Effects of 32-year leisure time physical activity discordance in twin pairs on health (TWINACTIVE study): aims, design and results for physical fitness.

AbstractThe physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic s…

Low-protein vegetarian diet does not have a short-term effect on blood acid–base status but raises oxygen consumption during submaximal cycling

Abstract Background Acid–base balance refers to the equilibrium between acids and bases in the human body. Nutrition may affect acid–base balance and further physical performance. With the help of PRAL (potential renal acid load), a low-protein vegetarian diet (LPVD) was designed to enhance the production of bases in body. The aim of this study was to investigate if LPVD has an effect on blood acid–base status and performance during submaximal and maximal aerobic cycling. Methods Nine healthy, recreationally active men (age 23.5 ± 3.4 yr) participated in the study and were randomly divided into two groups in a cross-over study design. Group 1 followed LPVD for 4 days and group 2 ate normall…

Blocking of myostatin and activins increase muscle protein synthesis and mTORC1 signaling but decreases capillary density

Correction: DAPIT Over-Expression Modulates Glucose Metabolism and Cell Behaviour in HEK293T Cells

Introduction Diabetes Associated Protein in Insulin-sensitive Tissues (DAPIT) is a subunit of mitochondrial ATP synthase and has also been found to associate with the vacuolar H+-ATPase. Its expression is particularly high in cells with elevated aerobic metabolism and in epithelial cells that actively transport nutrients and ions. Deletion of DAPIT is known to induce loss of mitochondrial ATP synthase but the effects of its over-expression are obscure. Results In order to study the consequences of high expression of DAPIT, we constructed a transgenic cell line that constitutively expressed DAPIT in human embryonal kidney cells, HEK293T. Enhanced DAPIT expression decreased mtDNA content and …

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 orig…

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

This cross-sectional study of young Finnish men examines the associations of aerobic fitness and muscular strength with metabolome measures that are associated with cardiometabolic risks.

Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained

Key points Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents. Little is known about the effects of high-intensity interval training (HIT) or of purely anaerobic resistance training on AHN. Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats. We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity. Our results confirm that sustained aerobic exercise is key in improving AHN. Abstract Aerobic exercise, such as running, has positive effects on brain …

Intrinsic aerobic capacity governs the associations between gut microbiota composition and fat metabolism age-dependently in rat siblings

Host genetic factors affecting the gut microbiome play an important role in obesity, yet limited attention has been paid on the host genetic factors linked to physical fitness in modifying the microbiome. This study determined whether sibling-matched pairs of rats selectively bred for high (HCR) and low (LCR) aerobic capacity differ in their microbiome age-dependently and which taxa associate with differential in metabolism. Several taxa in young adult rats (hereafter young) linked to inherited aerobic capacity, while in older adult (hereafter old) rats most of the differences between the lines associated with body weight. Despite the absence of weight differential between LCR and HCR when…

Amorphous and crystalline polyetheretherketone: Mechanical properties and tissue reactions during a 3-year follow-up.

The study was aimed to test the mechanical strength, structural stability, and tissue reactions of optically amorphous and crystalline polyetheretherketone (PEEK) plates during a 3-year follow-up in vivo and in vitro. The injection-moulded PEEK plates were implanted to the dorsal subcutis of 12 sheep, which were sacrificed at 6-156 weeks. Thereafter, the plates were subjected to tensile tests, and levels of crystallinity were assessed by differential scanning calorimetry (DSC). Histological evaluation was carried out using the paraffin technique. In vitro properties were examined with the tensile test and DSC at 0-156 weeks. Tissue reactions were mild and fairly similar for the amorphous an…

SAP30L interacts with members of the Sin3A corepressor complex and targets Sin3A to the nucleolus.

Histone acetylation plays a key role in the regulation of gene expression. The chromatin structure and accessibility of genes to transcription factors is regulated by enzymes that acetylate and deacetylate histones. The Sin3A corepressor complex recruits histone deacetylases and in many cases represses transcription. Here, we report that SAP30L, a close homolog of Sin3-associated protein 30 (SAP30), interacts with several components of the Sin3A corepressor complex. We show that it binds to the PAH3/HID (Paired Amphipathic Helix 3/Histone deacetylase Interacting Domain) region of mouse Sin3A with residues 120–140 in the C-terminal part of the protein. We provide evidence that SAP30L induces…

Vitamin E deficiency and the susceptibility to lipid peroxidation of mouse cardiac and skeletal muscles

Effects of a short-term vitamin E deficiency on some lipid peroxidative properties were investigated in mouse cardiac and skeletal muscles. The concentration of vitamin E decreased 35.8% in 5 weeks and 61.2% in 12 weeks in skeletal muscle. The corresponding decrease in cardiac muscle was 65.7% in 12 weeks. Simultaneously the susceptibility of muscle homogenates to in vitro lipid peroxidation increased with 48.6% (5 weeks) and 44.5% (12 weeks) in skeletal muscle and with 101.8% (12 weeks) in cardiac muscle. Highly significant negative correlations were observed between the concentration of vitamin E and in vitro lipid peroxidation in cardiac and skeletal muscles. Also the sensitivity to Fe2+…

Model ecosystem for environmental transport of xenobiotics

A compartmentalized aquatic-terrestrial flow-through model ecosystem was constructed for studying the transport of agricultural chemicals from the soil to the aquatic environment in soil drainage. Factors were investigated on the fate of reference toxicant,14C-DDT, in the subsystems of the model. The behavior of DDT corresponds to its behavior in natural soil/water systems. The soil, acting as a reservoir, retained most of the DDT. The transportation of DDT to the aquatic compartment was negligible, with low availability to the aquatic biota. Because of the dynamic nature of the model, variation was evident between and within model units.

Fyysinen aktiivisuus pitää yllä aivojenkin terveyttä ja toimintakykyä läpi elämän

Fyysisesti aktiivisilla ikääntyneillä ihmisillä on pienempi riski sairastua muistisairauksiin, kuten Alzheimerin tautiin, ja liikuntaa on ehdotettu jopa muistisairauksien hoidoksi. Positiivinen yhteys aerobisen kunnon ja aivojen rakenteellisen kunnon välillä näkyy vielä yli 80-vuotiailla. Liikunnan vaikutuksia aivojen terveyteen ja oppimisen edellytyksiin tutkitaan nyt monitieteellisesti ja -menetelmällisesti. nonPeerReviewed

Leisure-time physical activity and high-risk fat: a longitudinal population-based twin study.

Exercise is thought to reduce high-risk body fat, but intervention studies are frequently limited by short follow-ups and observational studies by genetic selection. Therefore, we studied the effects of a physically inactive vs active lifestyle on high-risk (visceral, liver and intramuscular) fat in twin pairs discordant for leisure-time physical activity habits for over 30 years.A longitudinal population-based twin study.Sixteen middle-aged (50-74 years) same-sex twin pairs (seven monozygotic (MZ), nine dizygotic (DZ)) with long-term discordance for physical activity habits were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in…

Long lasting high fat feeding increases the capillary density in the skeletal muscle of mice

Striated muscle-specific serine/threonine-protein kinase beta (SPEGβ) 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 stat…

Myocardial blood flow and adenosine A2Areceptor density in endurance athletes and untrained men

Previous human studies have shown divergent results concerning the effects of exercise training on myocardial blood flow (MBF) at rest or during adenosine-induced hyperaemia in humans. We studied whether these responses are related to alterations in adenosine A2A receptor (A2AR) density in the left-ventricular (LV) myocardium, size and work output of the athlete's heart, or to fitness level. MBF at baseline and during intravenous adenosine infusion, and A2AR density at baseline were measured using positron emission tomography, and by a novel A2AR tracer in 10 healthy male endurance athletes (ET) and 10 healthy untrained (UT) men. Structural LV parameters were measured with echocardiography.…

Effects of diet-induced obesity and voluntary wheel running on bone mechanical properties from male young C57/6J mice

Resistance exercise with whey protein ingestion affects mTOR signaling pathway and myostatin in men.

Signaling pathways sense local and systemic signals and regulate muscle hypertrophy. The effects of whey protein ingestion on acute and long-term signaling responses of resistance exercise are not well known. Previously untrained young men were randomized into protein ( n = 9), placebo ( n = 9), and control ( n = 11) groups. Vastus lateralis (VL) muscle biopsies were taken before and 1 h and 48 h after a leg press of 5 × 10 repetitions [resistance exercise (RE)] and after 21 wk (2 times per week) of resistance training (RT). Protein (15 g of whey) or nonenergetic placebo was ingested before and after a single RE bout and each RE workout throughout the RT. The protein group increased its bo…

Effect of diet composition on acid–base balance in adolescents, young adults and elderly at rest and during exercise

Diets rich in animal protein and cereal grains and deficient in vegetables and fruits may cause low-grade metabolic acidosis, which may impact exercise and health. We hypothesized that (1) a normal-protein diet with high amount of vegetables and fruits (HV) induces more alkaline acid-base balance compared with a high-protein diet with no vegetables and fruits (HP) and (2) diet composition has a greater impact on acid-base balance in the elderly (ELD).In all, 12-15 (adolescents (ADO)), 25-35 (young adults (YAD)) and 60-75 (ELD)-year-old male and female subjects (n=88) followed a 7-day HV and a 7-day HP in a randomized order and at the end performed incremental cycle ergometer tests. We inves…

Lysosomal changes related to ageing and physical exercise in mouse cardiac and skeletal muscles.

Physical exercise increased the activities of arylsulphatase, cathepsin D and β-glucuronidase in mouse skeletal muscle but not in cardiac muscle. Exercise-induced lysosomal response was more prominent in young adult than in senescent mice. The lipofuscin content of cardiac and skeletal muscles increased markedly during ageing and was also found to increase slightly after exertion in young mice, but not in senescent ones.

Are skeletal muscleFNDC5gene expression and irisin release regulated by exercise and related to health?

Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n = 17), (2) a heavy-intensity resistance exercise (RE) bout (young n = 10, older n = 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n = 9), or …

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. Furt…

iGEMS : an integrated model for identification of alternative exon usage events

DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with (n = 9) or without (n = 8) the anti-diabetes drug,…

Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autop…

Physical activity in adulthood: genes and mortality.

AbstractObservational studies report a strong inverse relationship between leisure-time physical activity and all-cause mortality. Despite suggestive evidence from population-based associations, scientists have not been able to show a beneficial effect of physical activity on the risk of death in controlled intervention studies among individuals who have been healthy at baseline. On the other hand, high cardiorespiratory fitness is known to be a strong predictor of reduced mortality, even more robust than physical activity level itself. Here, in both animals and/or human twins, we show that the same genetic factors influence physical activity levels, cardiorespiratory fitness and risk of de…

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 dua…

Effects of training on regional substrate oxidation in the hearts of ageing rats.

23-month-old male rats were trained by running for 20 weeks. The oxidation rates of succinate, glutamate+malate, palmitoylcarnitine, and pyruvate and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in the subendocardium and subepicardium and in the right ventricle. Regional differences of substrate oxidation rates in the myocardium of old sedentary or trained rats were less than in young rats, suggesting that regional differences in the cardiac work load disappear during ageing. Training did not improve oxidation rates, in contradiction to some previous results.

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.
 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 assesse…

Fat oxidation at rest and during exercise in male monozygotic twins

Abstract 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 quantif…

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 …

Regional glucose uptake and protein synthesis in isolated perfused rat hearts immediately after training and later

The effect of 10 weeks of running training and termination of training on the regional distribution of cardiac glucose uptake and protein synthesis were studied in isolated perfused hearts in male rats. The left ventricular glucose uptake in hearts from sedentary rats was 1.87 +/- 0.14 mumol/min per g protein (mean +/- SE), being about 30% higher in the subendocardial than in the subepicardial layer (p less than 0.05). The gradient of left ventricular glucose uptake was similar to the controls in the rats retired from training, but was absent in the trained animals. The altered transmural glucose uptake probably reflects differences in the adaptive response of various myocardial muscle laye…

Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle.

Blood and lymphatic vessels together form the circulatory system, allowing the passage of fluids and molecules within the body. Recently we showed that lymphatic capillaries are also found in the capillary bed of skeletal muscle. Exercise is known to induce angiogenesis in skeletal muscle, but it is not known whether exercise has effects on lymphangiogenesis or lymphangiogenic growth factors. We studied lymphatic vessel density and expression of the main lymphangiogenic growth factors VEGF-C and VEGF-D and their receptor VEGFR-3 in response to acute running exercise and endurance exercise training in the skeletal muscle of healthy and diabetic mice. VEGF-C mRNA expression increased after t…

Muscle protein synthesis, mTORC1/MAPK/Hippo signaling, and capillary density are altered by blocking of myostatin and activins

Loss of muscle mass and function occurs in various diseases. Myostatin blocking can attenuate muscle loss, but downstream signaling is not well known. Therefore, to elucidate associated signaling pathways, we used the soluble activin receptor IIb (sActRIIB-Fc) to block myostatin and activins in mice. Within 2 wk, the treatment rapidly increased muscle size as expected but decreased capillary density per area. sActRIIB-Fc increased muscle protein synthesis 1–2 days after the treatment correlating with enhanced mTORC1 signaling (phosphorylated rpS6 and S6K1, r = 0.8). Concurrently, increased REDD1 and eIF2Bε protein contents and phosphorylation of 4E-BP1 and AMPK was observed. In contrast, pr…

Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress

Protein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e. unfolded protein response (UPR), play key roles in proteostasis but their involvement in the pathology of DMD are largely unknown. Moreover, exercise and activin receptor IIB blocking are two strategies that may be beneficial to DMD muscle, but studies to examine their effects on these proteostasis pathways are lacking. Therefore, these pathways were examined in the muscle of mdx mice, …

Acute Metabolic Response, Energy Expenditure, and EMG Activity in Sitting and Standing

Purpose While merely standing up interrupts sedentary behavior, it is important to study acute metabolic responses during single bouts of sitting and standing to understand the physiological processes affecting the health of office workers. Methods Eighteen healthy middle-age women 49.4 ± 7.9 yr old (range: 40–64) with a body mass index of 23.4 ± 2.8 kg·m−2 volunteered for this laboratory-based randomized crossover trial where they performed 2 h desk work in either sitting or standing postures after overnight fasting. Muscle activity (normalized to walking at 5 km·h−1), respiratory gas exchange, and blood samples were assessed after glucose loading (75 g). Results Compared with seated work,…

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

Abstract 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 u…

Altered REDD1, myostatin, and Akt/mTOR/FoxO/MAPK signaling in streptozotocin-induced diabetic muscle atrophy

Type 1 diabetes, if poorly controlled, leads to skeletal muscle atrophy, decreasing the quality of life. We aimed to search highly responsive genes in diabetic muscle atrophy in a common diabetes model and to further characterize associated signaling pathways. Mice were killed 1, 3, or 5 wk after streptozotocin or control. Gene expression of calf muscles was analyzed using microarray and protein signaling with Western blotting. We identified translational repressor protein REDD1 (regulated in development and DNA damage responses) that increased seven- to eightfold and was associated with muscle atrophy in diabetes. The diabetes-induced increase in REDD1 was confirmed at the protein level. …

CHI3L1 - a novel myokine

Long-term Leisure-time Physical Activity and Serum Metabolome

Background— Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk. Methods and Results— Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their >30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 population-based cohorts (mean ages, 31–52 years) were also studied (1037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the …

Transmural distribution of biochemical markers of total protein and collagen synthesis, myocardial contraction speed and capillary density in the rat left ventricle in angiotensin II-induced hypertension.

The effect of angiotensin II-induced hypertension on selected biochemical parameters was studied in Sprague-Dawley rats. Angiotensin II infusion at rates of 41.7 micrograms h-1 kg-1 and 12.5 micrograms h-1 kg-1 for 2, 5, 10 and 15 days elevated the systolic blood pressure from 143 +/- 7 mmHg to 215-230 mmHg (P less than 0.001) and 185-195 mmHg (P less than 0.001), respectively. The left ventricular weight/body weight ratio increased 10-14% (P less than 0.05) and 23-32% (P less than 0.001) after 2-15 days in rats treated at the lower and higher infusion rates, respectively. Prolyl 4-hydroxylase (PH) activity, a marker of collagen synthesis, was evenly distributed in the left ventricle. PH ac…

Regional differences of substrate oxidation capacity in rat hearts: effects of extra load and endurance training.

Male rats, aged 17 weeks at the end of experiments, were divided into four groups. Two groups lived in normal cage conditions with or without extra load (20% of the body weight) and two groups were trained by running with or without extra load for 8 weeks. Oxidation rates of succinate, glutamate + malate, palmitoylcarnitine, and pyruvate, and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in homogenates of the right ventricle and in those of the subendocardial and subepicardial layers of the left ventricle. Oxidation rates of succinate and palmitoylcarnitine tended to be higher in the subendocardium than in the subepi…

In vivo and in vitro degradation of a novel bioactive guided tissue regeneration membrane

The aim of this study was to assess degradation of a novel bioactive guided tissue regeneration (GTR) membrane and to quantify the concurrent tissue responses. Pieces of membrane composed of poly-l-lactide, poly-d,l-lactide, trimethylenecarbonate and polyglycolide were dipped into an N-methyl-2-pyrroline (NMP) solution and implanted in the mandibles of 10 sheep. The animals were sacrificed at 6-104 weeks. Parallel in vitro degradation was analysed by measuring the inherent viscosity, water absorption and remaining mass. One of the 2 in vitro sets of membranes was prehandled with NMP. At 6-26 weeks in vivo, the gradually more degraded implants were surrounded by a fibrous network. At 52 and …

Increased prolyl 4-hydroxylase activity in the myocardium of endurance-trained mice.

Endurance training over 3, 10 or 20 days increased the activity of prolyl 4-hydroxylase (PH) in the left ventricle of mice. No increase was observed in the weight of the left ventricle, in galactosylhydroxylysyl glucosyltransferase activity or in hydroxyproline concentration. The increase in PH suggests that the synthesis of collagen increases during physiological adaptation of the heart to endurance exercise without changes in the ventricle weight or its total collagen content.

Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin blocked mdx mice

The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autoph…

Effects of diet-induced obesity and voluntary wheel running on the microstructure of the murine distal femur

Abstract Background Obesity and osteoporosis, two possibly related conditions, are rapidly expanding health concerns in modern society. Both of them are associated with sedentary life style and nutrition. To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (μCT) together with peripheral quantitative computed tomography (pQCT) to examine the microstructure of the distal femoral metaphysis in mice. Methods Forty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C), control + running (CR), high-fat diet (HF), and high-fat diet + running (HFR). After a 21-week intervention, all the mice were sacrifi…

TopoCell – An image analysis tool to study intracellular topography

Effect of chronic exercise on glucose uptake and activities of glycolytic enzymes measured regionally in rat heart.

Regional glucose uptake in perfused hearts, and the activities of several glycolytic enzymes contributing to the glucose metabolism in perfused and nonperfused hearts were studied in male and female rats after 8–9 weeks of swimming training. The left ventricular glucose uptake showed a transmural gradient in the sedentary animals, the subendocardial uptake being 30% and 12% higher than that of the subepicardial layer in the males and females, respectively. Swimming exercise abolished the left ventricular glucose uptake gradient in male rats, and in female rats an opposite gradient was found, the subepicardial uptake being 23% higher than the subendocardial uptake. The activities of phosphof…

Potential role of branched-chain amino acid catabolism in regulating fat oxidation.

Insulin-resistant or obese individuals have increased serum branched-chain amino acid (BCAA) levels. Recent findings relate increased BCAA catabolism to increased fatty acid oxidation and better metabolic health in physically active individuals. We hypothesize that, via glyceroneogenesis, BCAA catabolism mediates increased constitutive use of fatty acids for β-oxidation in subjects with increased inherent or acquired aerobic capacity both during exercise and at rest.

Rats selectively bred for low aerobic capacity become promptly fatigued and have slow metabolic recovery after stimulated muscle contractions

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 sel…

Effects of streptozotocin-induced diabetes, physical training and their combination on collagen biosynthesis in rat skeletal muscle.

The effects of streptozotocin-induced diabetes, physical training and their combination on the activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyl-transferase (GGT), both marker enzymes of collagen biosynthesis, and on the concentration of hydroxyproline (Hyp) were studied in vastus lateralis, rectus femoris and gastrocnemius muscles in rats. The experimental period was 12-16 weeks. Diabetes had an overall decreasing effect on specific PH activity in all muscles studied, whereas specific GGT activity remained at control level. Total PH and GGT activities decreased in all three muscles in the diabetic animals (P < 0.001). Training caused an increase in PH and GGT acti…

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

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…

Predictors of increase in physical activity during a 6-month follow-up period among overweight and physically inactive healthy young adults

Abstract Background/Objective The beneficial effects of physical activity (PA) are well known, but it remains challenging to increase PA among physically inactive and overweight young individuals. The present study aimed to examine how selected psychological and physical characteristics assessed at baseline predict the increase in total PA over a 6-month follow-up among 51 physically inactive and overweight adults (20 women, 31 men; age 26–40 years) who participated in a lifestyle counselling study without supervised PA sessions. Methods Baseline measurements included a questionnaire assessment of sense of coherence and psychological flexibility, heart rate monitoring-based stress/recovery …

Protein synthesis and cyclic GMP content in rat cardiac muscle after swimming exercise

Rats were exercised for 6 h by swimming. Phenylalanine incorporation into myocardial proteins was increased when 2 h had elapsed after the termination of exercise. Cyclic GMP concentration did not change during the experiment, which indicates that cyclic GMP does not act directly as a trigger of myocardial protein synthesis in volume overload.

Effects of high-fat diet and physical activity on pyruvate dehydrogenase kinase-4 in mouse skeletal muscle

Abstract Background The expression of PDK4 is elevated by diabetes, fasting and other conditions associated with the switch from the utilization of glucose to fatty acids as an energy source. It is previously shown that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a master regulator of energy metabolism, coactivates in cell lines pyruvate dehydrogenase kinase-4 (PDK4) gene expression via the estrogen-related receptor α (ERRα). We investigated the effects of long-term high-fat diet and physical activity on the expression of PDK4, PGC-1α and ERRα and the amount and function of mitochondria in skeletal muscle. Methods Insulin resistance was induced by a high-fat (HF) d…

Endurance training and antioxidants of lung

Mice and rats were adjusted to daily treadmill training programs, which were heavy enough to increase the oxidative capacity of skeletal muscles. Endurance training did not affect the activities of catalase and glutathione peroxidase and the concentration of vitamin E in the lungs of mice and rats. Thus increased ventilation and oxygen utilization induced by exercise training do not modify lung antioxidants, in contrast to hyperoxia and hypoxia.

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

Abstract 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…

Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk

A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To probe this linkage, we utilized rat models of low and high intrinsic aerobic endurance running capacity that differ also in the risk for metabolic syndrome. We investigated in skeletal muscle gene-phenotype relationships that connect aerobic endurance capacity with metabolic disease risk factors. The study compared 12 high capacity runners (HCRs) and 12 low capacity runners (LCRs) from generation 18 of selection that differed by 615% for maximal treadmill endurance running capacity. On average, LCRs were heavier and had increased blood glucose, insulin, and triglycerides compared with HCRs. HCRs we…

Morphometry of myocardial apex in endurance-trained mice of different ages

Mitochondrial volume density, surface density of the outer mitochondrial membrane, the mean number and size of mitochondria, and the mean surface density of crista membranes together with the volume densities of myofibrils and sarcoplasmic space were morpho-metrically analyzed in cardiac muscle of two groups of sedentary control mice aged 3 and 7 months, and in two groups of mice trained either 1 month rather intensely or 4 months moderately. Of the calculated mitochondrial variables only the surface density of the outer mitochondrial membrane differed between the older controls and the older trained animals, the density being slightly smaller in the trained group. The myofibrillar volume d…

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

Abstract 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 (D2O) 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 D2O for 3 weeks. Femur diaphyses (FEM), tibia proximal (T‐PRO), and distal (T‐DIS) epiphyses‐metaphyses and tibia mid‐shaft diaphyses (T…

Leisure-time physical activity and artery lumen diameters: A monozygotic co-twin control study

Exercise is thought to increase the diameter of the conduit arteries supplying the muscles involved. We studied the effects of a physically active vs inactive lifestyle on artery diameters in monozygotic (MZ) twin pairs discordant over 30 years for leisure-time physical activity habits. In a population-based co-twin control study design, six middle-aged (50-65 years) same-sex MZ twin pairs with long-term discordance for physical activity were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in 1975 and the same co-twin remained significantly more active during the 32-year follow-up. The main outcomes were arterial lumen diameters …

Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model

Abstract Background The TGFβ1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFβ1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new play…

Physical Activity, Fitness, Glucose Homeostasis, and Brain Morphology in Twins

The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity.From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage …

Molecular adaptations of voltage-gated sodium ion channel related proteins after fatiguing stretch-shortening cycle exercise

Dystrophin associated protein alpha-syntrophin is known to interact with voltage-gated sodium ion channel (NaCh). Dystrophin is known to be sensitive to eccentric muscle actions. For this reason, the function of the NaChs might also be affected. Molecular adaptations of dystrophin, alpha-syntrophin and NaChs were investigated after fatiguing stretch-shortening cycle (SSC) exercise, which consisted of unilateral jumps on a sledge apparatus. Muscle biopsies were taken from the vastus lateralis muscle of eight healthy subjects immediately after (IA) and 2 days after (2D) the exercise to analyze mRNA levels and immunohistochemical staining patterns. SSC exercise resulted in decreased isometric …

Cellular and tissue expression of DAPIT, a phylogenetically conserved peptide

DAPIT (Diabetes Associated Protein in Insulin-sensitive Tissues) is a small, phylogenetically conserved, 58 amino acid peptide that was previously shown to be down-regulated at mRNA level in insulin-sensitive tissues of type 1 diabetes rats. In this study we characterize a custom made antibody against DAPIT and confirm the mitochondrial presence of DAPIT on cellular level. We also show that DAPIT is localized in lysosomes of HUVEC and HEK 293T cells. In addition, we describe the histological expression of DAPIT in several tissues of rat and man and show that it is highly expressed especially in cells with high aerobic metabolism and epithelial cells related to active transport of nutrients …

Selected enzyme activities in mouse cardiac muscle during training and terminated training

We studied the effects of running-training, heavy exercise and termination of training on the heart weight, the ratio heart to body weight and the cardiac muscle activities of actomyosin ATPase, citrate synthase, succinate dehydrogenase, cytochrome c oxidase, malate dehydrogenase, adenylate kinase and beta-glucuronidase with adult male NMRI-mice. Stable hypertrophy (6-7%), estimated by the ratio heart or ventricle weight to body weight, was achieved by 28 exercises and it was dependent on the running speed (20 vs. 25 m X min-1). The withdrawal of training for 5-61 days did not permanently decrease the heart weight or the heart to body weight ratio to the level of sedentary controls. The act…

Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs

High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50-74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing…

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 inter…

Cellular and tissue expression of DAPIT, a phylogenetically conserved peptide

DAPIT (Diabetes Associated Protein in Insulin-sensitive Tissues) is a small, phylogenetically conserved, 58 amino acid peptide that was previously shown to be down-regulated at mRNA level in insulin-sensitive tissues of type 1 diabetes rats. In this study we characterize a custom made antibody against DAPIT and confirm the mitochondrial presence of DAPIT on cellular level. We also show that DAPIT is localized in lysosomes of HUVEC and HEK 293T cells. In addition, we describe the histological expression of DAPIT in several tissues of rat and man and show that it is highly expressed especially in cells with high aerobic metabolism and epithelial cells related to active transport of nutrients …

Effects of diet-induced obesity and voluntary wheel running on the microstructure of the murine distal femur

Background. Obesity and osteoporosis, two possibly related conditions, are rapidly expanding health concerns in modern society. Both of them are associated with sedentary life style and nutrition. To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (μCT) together with peripheral quantitative computed tomography (pQCT) to examine the microstructure of the distal femoral metaphysis in mice. Methods. Forty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C), control + running (CR), high-fat diet (HF), and high-fat diet + running (HFR). After a 21-week intervention, all the mice were sacrificed and…

Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model

Background. The TGFβ1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFβ1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new players in e…

Low-protein vegetarian diet does not have a short-term effect on blood acid¿base status but raises oxygen consumption during submaximal cycling

Background. Acid–base balance refers to the equilibrium between acids and bases in the human body. Nutrition may affect acid–base balance and further physical performance. With the help of PRAL (potential renal acid load), a low-protein vegetarian diet (LPVD) was designed to enhance the production of bases in body. The aim of this study was to investigate if LPVD has an effect on blood acid–base status and performance during submaximal and maximal aerobic cycling. Methods. Nine healthy, recreationally active men (age 23.5 ± 3.4 yr) participated in the study and were randomly divided into two groups in a cross-over study design. Group 1 followed LPVD for 4 days and group 2 ate normally (ND) …