Sedentary Conditions Research Articles

Concentrations of Ca, Mg, P, Prostaglandin E2 in Bones and Parathyroid Hormone; 1,25-dihydroxyvitamin D3; 17-β-estradiol; Testosterone and Somatotropin in Plasma of Aging Rats Subjected to Physical Training in Cold Water

Exposure to low temperatures can be considered a stressor, which when applied for a specific time can lead to adaptive reactions. In our study we hypothesized that cold, when applied to the entire body, may be a factor that positively modifies the aging process of bones by improving the mechanisms related to the body’s mineral balance. Taking the above into account, the aim of the study was to determine the concentration of calcium (Ca), magnesium (Mg), and phosphorus (P) in bones, and to examine bone density and concentrations of the key hormones for bone metabolism, namely parathyroid hormone (PTH), somatotropin (GH), 1,25-dihydroxyvitamin D3, 17-β estradiol, testosterone (T) in plasma, and prostaglandin E2 (PGE2) in the bone of aging rats subjected to physical training in cold water. The animals in the experiment were subjected to a series of swimming sessions for nine weeks. Study group animals (male and female respectively) performed swimming training in cold water at 5 ± 2 °C and in water with thermal comfort temperature (36 ± 2 °C). Control animals were kept in a sedentary condition. Immersion in cold water affects bone mineral metabolism in aging rats by changing the concentration of Ca, Mg, and P in the bone, altering bone mineral density and the concentration of key hormones involved in the regulation of bone mineral metabolism. The effect of cold-water immersion may be gender-dependent. In females, it decreases Ca and Mg content in bones while increasing bone density and 17-β estradiol and 1,25-dihydroxyvitamin D3 levels, and with a longer perspective in aging animals may be positive not only for bone health but also other estrogen-dependent tissues. In males, cold water swimming decreased PTH and PGE2 which resulted in a decrease in phosphorus content in bones (with no effect on bone density), an increase in 1,25-dihydroxyvitamin D3, and increase in T and GH, and may have positive consequences especially in bones and muscle tissue for the prevention of elderly sarcopenia.

Control of Protein and Energy Metabolism in the Pituitary Gland in Response to Three-Week Running Training in Adult Male Mice.

It is assumed that crosstalk of central and peripheral tissues plays a role in the adaptive response to physical activity and exercise. Here, we wanted to study the effects of training and genetic predisposition in a marathon mouse model on mRNA expression in the pituitary gland. Therefore, we used a mouse model developed by phenotype selection for superior running performance (DUhTP) and non-inbred control mice (DUC). Both mouse lines underwent treadmill training for three weeks or were kept in a sedentary condition. In all groups, total RNA was isolated from the pituitary gland and sequenced. Molecular pathway analysis was performed by ingenuity pathway analysis (IPA). Training induced differential expression of 637 genes (DEGs) in DUC but only 50 DEGs in DUhTP mice. Genetic selection for enhanced running performance strongly affected gene expression in the pituitary gland and identified 1732 DEGs in sedentary DUC versus DUhTP mice. Training appeared to have an even stronger effect on gene expression in both lines and comparatively revealed 3828 DEGs in the pituitary gland. From the list of DEGs in all experimental groups, candidate genes were extracted by comparison with published genomic regions with significant effects on training responses in mice. Bioinformatic modeling revealed induction and coordinated expression of the pathways for ribosome synthesis and oxidative phosphorylation in DUC mice. By contrast, DUhTP mice were resistant to the positive effects of three-week training on protein and energy metabolism in the pituitary gland.

Printed Iontophoretic‐Integrated Wearable Microfluidic Sweat‐Sensing Patch for On‐Demand Point‐Of‐Care Sweat Analysis

AbstractIn recent years, wearable epidermal sweat sensors have received extensive attention owing to their great potential to provide personalized information on the health status of individuals at the molecular level. For on‐demand medical analysis of sweat in sedentary conditions, a cost‐effective wearable integrated platform combining sweat stimulation, sampling, transport, and analysis is highly desirable. In this work, a printed iontophoretic system integrated into a microfluidic sensing platform, which combines sweat induction, collection, and real‐time analysis of sweat‐ions into a single patch for on‐demand sweat monitoring on human subjects in stationary conditions is reported. The incorporation of microfluidics features facilitates sweat sampling, collection, and guiding through capillary effect. The multisensing sensor array exhibits sensitivity close to Nernstian behavior for sodium, potassium, and pH. The correlation between the concentrations of ions measured with the sweat patch and with ion chromatography analysis demonstrates the applicability of the system for real‐time point‐of‐care monitoring of the health status of individuals. Furthermore, the sweat patch electronic interface with wireless transmission enables real‐time data monitoring and storage over a cloud platform. This printed iontophoretic‐integrated fluidic sweat patch provides a cost‐effective solution for the on‐demand analysis of sweat components for healthcare applications.

Reduced metabolic efficiency in sedentary eucaloric conditions predicts greater weight regain in adults with obesity following sustained weight loss.

BackgroundSuccessful long-term weight loss maintenance after caloric restriction (CR) is rarely achieved. Besides known metabolic, behavioral, and cognitive factors, 24-hour energy expenditure (24hEE) relative to body size (i.e., metabolic efficiency) might influence subsequent weight loss maintenance.MethodsEleven participants with obesity (BMI=39.0±8.7 kg/m2, body fat=36.1±6.4%) had 24hEE measured in a whole-room indirect calorimeter during eucaloric conditions and weight stability prior to starting a 6-week inpatient CR study (50% of daily energy needs). Twenty-four-hour energy expenditure was adjusted via regression analysis for fat free mass (FFM) and fat mass (FM) by DXA. Body composition was reassessed at the end of CR and after 1-year follow-up. Free-living weight was assessed by monthly weight measurements during 12 months.ResultsAfter 6-week CR, participants lost 8.5±2.7% weight (FFM: −6.3±3.6 kg, FM: −3.4±1.2 kg) but regained 5.1±8.0% one year following CR, which was mostly due to FFM regain (+5.7±5.5 kg) and unchanged FM. A relatively higher 24hEE by 100 kcal/day prior to CR was associated with an average greater rate of weight regain by +0.3 kg/month during follow-up and a greater final weight regain by +5.1 kg after 1 year of follow-up.ConclusionThese results suggest that reduced metabolic efficiency in 24hEE during eucaloric, sedentary conditions may predict greater weight regain after CR-induced weight loss.

Study on the Wearing Performance of Compression Stockings and Its Influence on the Blood Flow Velocity of Lower Limbs

Compression stockings can reduce venous pressure and improve venous return by applying progressive pressure on the lower limbs from bottom to top, thereby preventing and treating venous diseases of the lower limbs. The purpose of this research is to conduct a preliminary understanding and analysis of compression stockings through various mechanical properties and feel styles of compression stockings, and to explore the effect of compression stockings on the blood flow of lower limbs by using blood flow speed as an experimental index. The results show that low-grade compression stockings are more effective in accelerating blood flow in healthy people under sedentary conditions.

The Effects of Continuous and Withdrawal Voluntary Wheel Running Exercise on the Expression of Senescence-Related Genes in the Visceral Adipose Tissue of Young Mice.

Obesity has become a global medical problem. The upregulation of senescence-related markers in adipose tissue may cause impairment of adipose tissue and disorders of systemic metabolism. Weight control through diet has been found to ameliorate senescence in the adipose tissue. Exercise is also important in maintaining a healthy lifestyle, however, very few researchers have examined the relationship between senescence-related markers in adipose tissue. Dietary restriction is also reported to have a legacy effect, wherein the effects are maintained for some periods after the termination of the intervention. However, very few researchers have examined the relationship between exercise and senescence-related markers in adipose tissue. Besides, there is no study on the long-term effects of exercise. Hence, we investigated whether the exercise could change the expression of senescence-related genes in the visceral adipose tissue of young mice and whether there was a legacy effect of exercise for 10 weeks after the termination of exercise. Four-week-old male ICR mice were assigned to one of the three groups: 20 weeks of sedentary condition, 20 weeks of voluntary wheel running exercise, or 10 weeks of exercise followed by 10 weeks of sedentary condition. The mice showed decreased expression in genes related to senescence and senescence-associated secretory phenotype, such as p53, p16, and IL-6, in the visceral adipose tissue in response to exercise. These effects were maintained for 10 weeks after the mice stopped exercising. Our study is the first report that exercise reduces the expression of senescence-related genes in the visceral adipose tissue of young mice, and that exercise causes the legacy effect.

Influence of Obesity and Exercise on β2-Adrenergic-Mediated Anti-Inflammatory Effects in Peritoneal Murine Macrophages

Obesity is a chronic low-grade inflammatory condition, and β2-adrenergic agonists as well as exercise have been proposed as anti-inflammatory strategies in obesity, so it is critical to accurately determine the effects of β2-adrenergic stimulation, especially when combined with other non-pharmacological therapies. The aim of this investigation was to determine the effect of β2-adrenergic activation on the inflammatory profile and phenotype of macrophages, and whether these effects could be affected by obesity and exercise in this condition. High-fat diet-induced obese and lean C57BL/6J mice were allocated to sedentary or exercised groups. The inflammatory profiles and phenotypes of their peritoneal macrophages were assessed by flow cytometry in the presence or absence of the selective β2-adrenergic receptor agonist terbutaline. β2-adrenergic activation caused global phenotypic anti-inflammatory effects in lean and obese sedentary mice, which were more drastic (also including anti-inflammatory effects on the cytokine profile) in obese animals. In exercised lean and obese animals, this anti-inflammatory effect is weaker and only evident by decreased iNOS and IL-8 expression, without changes in the anti-inflammatory markers. Therefore, β2-adrenergic activation leads to anti-inflammatory effects, but these effects are modulated by obesity in sedentary conditions, as well as by regular exercise; but not by obesity in trained conditions.

Constitutive PGC-1\u03b1 Overexpression in Skeletal Muscle Does Not Contribute to Exercise-Induced Neurogenesis

Physical exercise can improve age-dependent decline in cognition, which in rodent is partly mediated by restoration of an age-dependent decline in neurogenesis. Exercise-inducible myokines in the circulation present a link in muscle-brain crosstalk. The transcription factor PGC-1α regulates the release of such myokines with neurotrophic properties into the circulation. We study how chronic muscular overexpression of PGC-1α could contribute to exercise-induced effects on hippocampal neurogenesis and if this effect could be enhanced in a running wheel paradigm. We used 3- and 11-month-old transgenic mice with overexpression of PGC-1α under the control of muscle creatinine kinase promoter (MCK-PGC-1α), which have a constitutively developed endurance muscle phenotype. Wild-type and MCK-PGC-1α mice were single housed with free access to running wheels. Four weeks of running in female animals increased the levels of newborn cells, immature neurons, and, for young animals, new mature neurons, compared to sedentary controls. However, no difference in these parameters was observed between wild-type and transgenic mice under sedentary or running conditions. Multiplex analysis of serum cytokines, chemokines, and myokines suggested several differences in serum protein concentrations between genotypes with musclin found to be significantly upregulated 4-fold in male MCK-PGC-1α animals. We conclude that constitutive muscular overexpression of PGC-1α, despite systemic changes and difference in serum composition, does not translate into exercise-induced effects on hippocampal neurogenesis, independent of the age of the animal. This suggests that chronic activation of PGC-1α in skeletal muscle is by itself not sufficient to mimic exercise-induced effects or to prevent decline of neurogenesis in aging.

Sedentary conditions during the lockdown and movement opportunities for the Italian elderly

The active lifestyle benefits are recognized for all age groups. In the over 65 year’s old population, the advantages deriving from active lifestyles and from the increase in the levels of physical activity assume particular relevance especially for the aging effect contrast. The effects of aging, in fact, involve all systems and all systems and can be counteracted by adopting active lifestyles the measures to combat the contagion have been progressive, from 8 March to 11 March and have disciplined and conditioned numerous individual and collective behaviors. The subsequent closure of parks, gardens and equipped green areas prevented the use of these spaces for recreational motor activity or for walking. The purpose of this study is to describe the strategies adopted and the motor tasks identified in a particular period of limitation of individual and group travel for the over 65 years old population. The motor skills to be solicited must meet two criteria: they must be related to the daily life and senior independence skills; they must be identified among those most affected by a period of forced suspension of activities or forced sedentary lifestyle.

Aerobic Exercise Counteracts Mitochondrial Dysfunction In The Insulin Resistant Brain

Insulin resistance (IR) increases the risk for Alzheimer’s disease and other dementias; however, the underpinning mechanisms for this increased risk remain to be fully defined. Impaired mitochondrial function is one component contributing to cognitive impairment. PURPOSE: As insulin resistance impairs mitochondrial oxidative metabolism and increases reactive oxygen species (ROS) in skeletal muscle, we considered whether similar events occur in the brain, which like muscle is rich in insulin receptors and mitochondria. Further, we sought to determine whether aerobic exercise (AE) could prevent the hypothesized deficits in mitochondrial function accompanying diet-induced IR. METHODS: 12-week-old, male, C57BL6 mice were fed a standard (Chow) or high fat diet (HFD) (60% kcal from fat) for four-weeks and provided access to running wheels (EX) or sedentary (SED) conditions (n = 9-10 per group). Following treatment, mitochondria were freshly isolated from the cerebrum to assess mitochondrial respiration, ROS production, and ATP production. Insulin resistance was determined ex-vivo in the hippocampus by the ability of insulin to stimulate AKT-phosphorylation. mtDNA copy number, mRNA expression, and proteomic measurements were performed on isolated hippocampal tissue. RESULTS: HFD induced hippocampal insulin resistance (p < 0.001), which was corrected by AE. HFD decreased ATP production 12% (p = 0.01) and increased ROS emission 79% (p < 0.01) in isolated cerebral mitochondria, which were rescued with AE. Impairments in mitochondrial function with HFD were paralleled by reductions in mtDNA copy number (1.00 ± 0.06 vs 0.85 ± 0.06; p = 0.02) and mRNA expression of mitochondrial genes, such as PGC1a1 (1.00 ± 0.05 vs 0.78 ± 0.07; p = 0.03) and TFAM (1.00 ± 0.08 vs 0.62 ± 0.11; p = 0.03), which were corrected by AE. Proteomic analysis of the hippocampus showed that HFD led to oxidative post-translational modifications (PTMs) to 17 mitochondrial proteins (corrected p-value ≤ 0.05 and absolute log2 fold change ≥ 0.5); however, this increase in oxidative PTMs to mitochondrial proteins with HFD was almost completely reversed by AE. CONCLUSIONS: HFD induces IR in the cerebrum and hippocampus, which associates with mitochondrial dysfunction. Brain IR and mitochondrial dysfunction accompanying HFD are prevented with AE.

Vascular Protection by Exercise in Obesity: Inflammasome-associated Mechanisms.

The nodlike receptor family pyrin domain containing 3 (NLRP3) inflammasome is a critical player in vascular pathology as it regulates caspase-1-mediated interleukin (IL)-1β processing. Physical activity ameliorates obesity-induced inflammation and vascular dysfunction, but the mechanisms responsible for these positive changes are incompletely understood. Here, the protective effect of physical activity on the inflammasome-associated vascular dysfunction in obesity and its putative mechanisms were investigated. Mice were fed a control low-fat diet (LFD) or a high-fat diet (HFD; 45% of calories from fat) and provided with running wheel access (LF-RUN or HF-RUN) or denied wheel access for our sedentary condition (LF-SED or HF-SED). The NLRP3 inflammasome-associated pathway, including NLRP3, caspase-1, and IL-1β, in mice aorta was examined by RT-qPCR and FLICA and DAB staining. The protein expression of zonula occluden-1 (ZO-1), ZO-2, adiponectin (APN), and adiponectin receptor 1 (AdipoR1) in aortic endothelial cells was determined by immunofluorescence double staining. Intracellular reactive oxidative stress and nitric oxide (NO) production were monitored with fluorescence probes, dihydroethidium, and diaminofluorecein. HFD increased caspase-1 and IL-1β at mRNA and protein levels in endothelial cells of the aorta, and this was attenuated by voluntary running. HFD decreased ZO-1 and ZO-2 expression and reduced APN and AdipoR1 signaling; these were restored by running. The elevated intracellular superoxide (O2) production observed in HF-SED was ameliorated in HF-RUN. Finally, HF-RUN improved NO production in the aorta compared with HF-SED. Our findings suggest that voluntary running ameliorates mechanisms associated with vascular dysfunction by suppressing NLRP3 inflammasome, improving NO production, and reducing oxidative stress. Such benefits of physical activity may be, at least in part, associated with APN-AdipoR1 signaling and tight junction protein expression.

Host genotype and exercise exhibit species-level selection for members of the gut bacterial communities in the mouse digestive system

The mammalian gut microbiome can potentially impact host health and disease state. It is known that the mouse-genome, eating-behavior, and exercise-status promotes higher taxonomic rank-level alterations (e.g. family to phyla-level) of the gut microbiota. Here, host genotype or activity status was investigated to determine if selection of individual bacterial species or strains could be discerned within the murine digestive system. For this study, the fecal bacterial community of adenylyl cyclase 5 knock-out (AC5KO, n = 7) mice or their wild-type (WT, n = 10) littermates under exercise or sedentary conditions were profiled by sequencing rRNA operons. AC5KO mice were chosen since this genotype displays enhanced longevity/exercise capacity and protects against cardiovascular/metabolic disease. Profiling of rRNA operons using the Oxford MinION yielded 65,706 2-D sequences (after size selection of 3.7–5.7 kb) which were screened against an NCBI 16S rRNA gene database. These sequences were binned into 1,566 different best BLAST hits (BBHs) and counted for each mouse sample. Non-metric multidimensional scaling (NMDS) of the gut microbial community demonstrated clustering by physical activity (p = 0.001) but not by host genotype. Additionally, sequence similarity and phylogenetic analysis demonstrated that different bacterial species (closely related to Muribaculum intestinale and Parasutterella excrementihominis) inhabit AC5KO or WT mice depending on activity status. Other bacterial species of the gut microbiota did not follow such patterning (e.g. Turicibacter sanguinis and Turicimonas muris). Our results support the need of improved taxonomic resolution for better characterization of bacterial communities to deepen our understanding of the role of the gut microbiome on host health.

Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development

Accumulative evidence links breast cancer development to excess weight and obesity. During obesity, dysregulations of adipose tissue induce an increase in pro-inflammatory adipokine secretions, such as leptin and oestrogen secretions. Furthermore, a raise in oxidative stress, along with a decrease in antioxidant capacity, induces and maintains chronic inflammation, which creates a permissive environment for cancer development. Physical activity is recommended as a non-pharmacological therapy in both obese and cancer situations. Physical activity is associated with a moderation of acute inflammation, higher antioxidant defences and adipokine regulation, linked to a decrease of tumour-cell proliferation. However, the biological mechanisms underlying the relationship between oxidative stress, low-grade inflammation, carcinogenesis, obesity and physical activity are poorly understood. Our study is based on old, ovariectomised mice (C57BL/6J mice, 33 weeks old), fed with a high fat diet which increases adipose tissue favouring overweight and obesity, and housed in either an enriched environment, promoting physical activity and social interactions, or a standard environment constituting close to sedentary conditions. Our model of mammary carcinogenesis allowed for the exploration of tissue secretions and signalling pathway activation as well as the oxidative status in tumours to clarify the mechanisms involved in a multiple factorial analysis of the data set. The multiple factorial analysis demonstrated that the most important variables linked to moderate, spontaneous physical activity were the increase in growth factor (epithelial growth factor (EGF), hepatocyte growth factor (HGF)) and the activation of the signalling pathways (STAT3, c-jun n-terminal kinases (JNK), EKR1/2, nuclear factor-kappa B (NF-κB)) in the gastrocnemius (G). In inguinal adipose tissue, the NF-κB inflammation pathway was activated, increasing the IL-6 content. The adiponectin plasma (P) level increased and presented an inverse correlation with tumour oxidative status. Altogether, these results demonstrated that spontaneous physical activity in obesity conditions could slow down tumour growth through crosstalk between muscle, adipose tissue and tumour. A spontaneous moderate physical activity was able to modify the inter-organ exchange in a paracrine manner. The different tissues changed their signalling pathways and adipokine/cytokine secretions, such as adiponectin and leptin, resulting in a decrease in anti-oxidative response and inflammation in the tumour environment. This model showed that moderate, spontaneous physical activity suppresses tumour growth via a dialogue between the organs close to the tumour.

Proteomic Analysis of Myocardia Containing the Obscurin R4344Q Mutation Linked to Hypertrophic Cardiomyopathy.

Obscurin is a giant cytoskeletal protein with structural and regulatory roles encoded by the OBSCN gene. Recently, mutations in OBSCN were associated with the development of different forms of cardiomyopathies, including hypertrophic cardiomyopathy (HCM). We previously reported that homozygous mice carrying the HCM-linked R4344Q obscurin mutation develop arrhythmia by 1-year of age under sedentary conditions characterized by increased heart rate, frequent incidents of premature ventricular contractions, and episodes of spontaneous ventricular tachycardia. In an effort to delineate the molecular mechanisms that contribute to the observed arrhythmic phenotype, we subjected protein lysates prepared from left ventricles of 1-year old R4344Q and wild-type mice to comparative proteomics analysis using tandem mass spectrometry; raw data are available via ProteomeXchange with identifier PXD017314. We found that the expression levels of proteins involved in cardiac function and disease, cytoskeletal organization, electropotential regulation, molecular transport and metabolism were significantly altered. Moreover, phospho-proteomic evaluation revealed changes in the phosphorylation profile of Ca2+ cycling proteins, including sAnk1.5, a major binding partner of obscurin localized in the sarcoplasmic reticulum; notably, this is the first report indicating that sAnk1 undergoes phosphorylation. Taken together, our findings implicate obscurin in diverse cellular processes within the myocardium, which is consistent with its multiple binding partners, localization in different subcellular compartments, and disease association.

Augmented Cardiac Mitochondrial Capacity in High Aerobic Capacity “Disease Resistant” Phenotype at Rest is Lost Following Ischemia Reperfusion

RationaleIschemic heart disease is a major cause of morbidity. Regular active exercise is therapeutic, but up to 70% of individual exercise capacity is due to an intrinsic genetic component. Intrinsic capacity can be studied using high (HCR) and low (LCR) aerobic running capacity rat strains. The phenotypes differ by more than 5 fold in sedentary average running distance and time. The HCR rats have been characterized as “disease resistant”, while the LCRs are characterized as “disease prone”. A consistent characteristic of the LCR is reduced metabolic capacity in several tissues, but metabolic capacity in cardiac tissue is not well studied in these phenotypes, particularly following the metabolic stress of ischemia and reperfusion.Methods32 HCR and LCR rats were obtained from the parent colony at the University of Toledo, housed under sedentary conditions, and fed normal chow. LCR and HCR animals were randomly assigned to either control (C, n = 8 each) or ischemia reperfusion (IR, n = 8 each). On each study day, one HCR/LCR pair was anesthetized and hearts were rapidly excised. In IR animals, the hearts were immediately flushed with iced hyperkalemic, hyperosmotic, cardioplegia solution, and subjected to cold global ischemic arrest (80 min). Following arrest, the hearts underwent warm reperfusion (120 min) using a Langendorff style perfusion system. Following reperfusion, the heart was weighed and the LV was isolated. A mid ventricular ring was obtained to estimate infarction size (TTC), and part of the remaining tissue (~150 mg) was transferred to homogenation buffer on ice. Isolated mitochondria (MITO) samples were prepared and used to determine respiratory capacity under different metabolic conditions (OROBOROS). MITO from control animals were obtained and prepared in similar fashion, but immediately following anesthesia and heart removal, and without IR. Citrate synthase activity was measured in each sample.ResultsIn the control rats, HCR MITO showed respiratory rates 32% higher at rest and more than 40% higher under maximally stimulated conditions, compared to LCR MITO (both p &lt; 0.05). After IR, resting MITO respiratory rates were decreased to about 10% in both strains, and the augmented capacity in HCRs was absent. Maximally stimulated rates also were decreased more than 50% from control, and were no longer different between phenotypes. Infarct size was not significantly different between HCR and LCR (49.2% ± 5.6 vs. 53.7% ± 4.9), nor was average coronary flow during reperfusion.ConclusionCardiac mitochondria from HCR were significantly higher in control conditions with each substrate tested. After IR insult, the cardiac mitochondrial respiratory rates were similar between phenotypes, as was infract size. Relatively, the loss of respiratory capacity was actually greater in HCR than LCR. Together, these data could suggest limits in the extent to which the HCR phenotype might be “protective” against acute tissue stressors. The extent to which any of these deficits could be “rescued” by an active exercise component is unknown.

Sex Differences and Inactivity In Rats Determine the Progression of Increased Sympathetic Activity Over Time.

Cardiovascular disease (CVD) is the leading cause of death, with males having a higher risk than females; that is, until menopause, when the risks reverse. Risk factors for CVD include a sedentary lifestyle as well as elevated sympathetic nerve activity (SNA). In women, resting SNA is influenced by the menstrual cycle; however, the interaction between sedentary conditions and the presence or absence of the female reproductive cycle on baseline sympathetic nerve activity is unknown. Therefore, the purpose of this study was to determine the effects of sedentary versus active conditions on resting SNA in male and female rats over time. In particular, we studied rats at four and eight weeks of age (i.e. before and after the onset of the estrous cycle, respectively in female rats). We hypothesized that time‐dependent increases in SNA in sedentary male rats would be offset by four weeks of voluntary exercise (running wheels) and attenuated in sedentary female rats due to the onset of the estrous cycle. We recorded splanchnic SNA from 32 rats under Inactin anesthesia and determined SNA action potential frequency according to Tan et al., (2009). Using a two‐way analysis of variance (ANOVA), with sex and condition as main effects, we found that four week‐old male rats exhibited lower SNA compared to eight week‐old sedentary males (42.0 ±6.3 Hz vs. 62.4 ±5.8 Hz; p=0.015; n=6 each), while exhibiting no significant difference from eight week‐old active males (37.4 ±6.1 Hz; p=0.003; n=7). In contrast, SNA was not significantly different between four week‐old females (54.6 ±4.5 Hz; n=4) and eight week‐old sedentary females (46.0 ±4.3 Hz; p=0.348; n=5), suggesting a lack of inactivity‐related increases in SNA as observed in males. SNA in four week‐old females was also not significantly different than eight week‐old active females (51.0 ±5.8 Hz; p=0.708; n=4). Our results suggest a sedentary lifestyle promotes increases in SNA over time in males but not females, due to physical inactivity in males and a protective effect of ovarian hormones in females. Male sex‐ and inactivity‐dependent increases in SNA likely play an important role in the higher risks of CVD observed in males compared to females.Support or Funding Information(NIH HL096787‐08; AHA25810010)

β-Alanine and l-histidine supplementation associated with combined training increased functional capacity and maximum strength in heart failure rats.

What is the central question of the study? Does β-alanine with l-histidine supplementation associated with endurance and strength training improve echocardiographic parameters, functional capacity, and maximum strength in rats with chronic heart failure? What is the main finding and its importance? β-Alanine with l-histidine supplementation associated with endurance and strength training increased functional capacity and maximum strength through increasing exercise capacity peripherally but did not affect echocardiographic parameters in rats with chronic heart failure. Combined training (CT) has been associated with positive responses in the clinical status of patients with chronic heart failure (CHF). Other non-pharmacological tools, such as amino acid supplementation, may further enhance its adaptation. However, the effects of β-alanine and l-histidine supplementation in CHF remain unclear. In the present study, the aim was to test whether supplementing carnosine precursors with CT could give improved responses in the functional capacity and echocardiographic variables of rats with CHF. Twenty-four Wistar rats, were submitted to myocardial infarction and allocated to three groups: animals with CHF kept in sedentary conditions (SED, n=8), animals with CHF submitted to CT in strength and aerobic exercise supplemented with placebo (CT-P, n=8) and animals with CHF submitted to CT in strength and aerobic exercise supplemented with β-alanine and l-histidine (CT-S, n=8). The trained animals were submitted to a strength protocol three times per week with intensity of 65-75% of one repetition maximum test. Aerobic training was conducted two times per week (50min, 15mmin-1 ). The supplemented group received β-alanine and l-histidine orally (each 250mgkg-1 day-1 ). No changes in echocardiographic and morphological parameters were found among the groups (P>0.05). Functional capacity, Δ and maximum strength were higher in CT-P than in SED and even higher in CT-S than in CT-P (P<0.01). The CT was able to improve functional capacity, but the supplementation was shown to enhance these parameters even further in the CHF rats. We conclude that the increase in functional capacity and strength gained through CT and supplementation were associated with the improvement in peripheral parameters with no changes in cardiac variables.

Moderate Exercise Modulates Tumor Metabolism of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) stands out for its aggressiveness and accelerated rate of proliferation. Evidence shows that exercise may exert antitumorigenic effects, but the biochemical mechanisms underlying them remain unclear. Our objective was to evaluate the ability of exercise to modulate tumor growth and energy metabolism in an experimental TNBC model. Female BALB/c mice were sedentary or trained for 12 weeks and inoculated with 1 × 104 4T1 cells in the eighth week. Analyzes of macronutrient oxidation, mitochondrial respiration, and expression of genes related to cell metabolism were performed. The results showed that the trained group had a smaller tumor mass and the mitochondria in the tumors presented lower respiratory rates in the state of maximum electron transport capacity. Additionally, the tumors of the exercised group showed a higher expression of genes related to tumor suppressors, while the genes linked with cellular growth were similar between groups. Furthermore, the training modulated the corporal macronutrient oxidation to almost exclusive carbohydrate oxidation, while the sedentary condition metabolized both carbohydrate and lipids. Therefore, the exercise reduced tumor growth, with an impact on mitochondrial and macronutrient metabolism. Our results shed light on the understanding of the antitumorigenic effects of physical exercise, particularly regarding the metabolic transformations in TNBC.

Estimating energy expenditure from accelerometer data in healthy adults and patients with type 2 diabetes.

The aim of this study was to develop specific prediction equations based on acceleration data measured at three body sites for estimating energy expenditure (EE) during static and active conditions in middle-aged and older adults with and without type 2 diabetes (T2D). Forty patients with T2D (age: 40-74yr, body mass index (BMI): 21-29.4kg·m-2) and healthy participants (age: 47-79yr, BMI: 20.2-29.8kg·m-2) completed trials in both static conditions and treadmill walking. For all trials, gas exchange was monitored using indirect calorimetry and vector magnitude was calculated from acceleration data measured using inertial measurement units placed to the participant's center of mass (CM), hip and ankle. Stepwise multiple regression analyses were conducted to select relevant variables to include in the three EE prediction equations, and three Monte Carlo cross-validation procedures were used to evaluate each separate equation. Vector magnitude (p<0.0001) and personal data (gender, diabetes status and BMI; p<0.0001) were used to develop three linear prediction equations to estimate EE during static conditions and walking. Cross-validation revealed similar robust coefficients of determination (R2: 0.81 to 0.85) and small bias (mean bias: 0.008 to -0.005kcal·min-1) for all three equations. However, the equation based on CM acceleration exhibited the lowest root mean square error (0.60kcal·min-1 vs. 0.65 and 0.69kcal·min-1 for the hip and ankle equations, respectively; p<0.001). The three equations based on acceleration data and participant characteristics accurately estimated EE during sedentary conditions and walking in middle-aged and older adults, with or without diabetes.

Acute after-school screen time in children decreases impulse control and activation toward high-calorie food stimuli in brain regions related to reward and attention.

The purpose of this study was to examine the effects of after-school sedentary screen time on children's brain activation in reward and cognitive control regions in response to pictures of high- and low-calorie foods. Thirty-two children participated in a randomized crossover study with counterbalanced treatment conditions. Conditions took place on separate days after school and included three hours of active or sedentary play. After each condition, neural activation was assessed using functional magnetic resonance imaging (fMRI) while participants completed a go/no-go task involving pictures of high- and low-calorie foods. General response inhibition was also measured using the Stroop task. Hunger was measured upon arrival to the testing facility and just prior to fMRI scans. Mixed effects models were used to evaluate main effects and interactions. Significant stimulus by condition interactions were found in the right superior parietal cortex, and left anterior cingulate cortex (Ps ≤ 0.05). High-calorie pictures elicited significantly more activation bilaterally in the orbitofrontal cortex compared to low-calorie pictures (Ps ≤ 0.05). Stroop task performance diminished significantly following the sedentary condition compared to the active (P ≤ 0.05). Subjective feelings of hunger were not different between conditions at any point. Sedentary screen time was associated with significantly decreased response inhibition and a reversed brain activation pattern to pictures of high- and low-calorie foods compared to active play, in areas of the brain important to the modulation of food intake. Decreased attention, and impulse control following sedentary screen time may contribute to disinhibited eating that can lead to overweight and obesity.