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Fructose-rich caloric sweeteners induce adverse changes in the metabolism of humans. The study evaluated the effects of high-intensity interval training (HIIT) on a fructose feeding model, focusing on the liver, white adipose tissue (WAT), skeletal muscle, and their interplay. Male C57BL/6 mice were fed for 18 wk one of the following diets: control (C; 5% of total energy from fructose) or fructose (F; 55% of total energy from fructose). In the 10th week, for an additional 8-wk period, the groups were divided into nontrained (NT) or HIIT groups, totaling four groups: C-NT, C-HIIT, F-NT, and F-HIIT. At the end of the experiment, fructose consumption in the F-NT group led to a high systolic blood pressure, high plasma triglycerides, insulin resistance with glucose intolerance, and lower insulin sensitivity. We also observed liver steatosis, adipocyte hypertrophy, and diminished gene expressions of peroxisome proliferator-activated receptor- coactivator 1-α and fibronectin type III domain containing 5 (FNDC5; irisin) in this F-NT group. These results were accompanied by decreased gene expressions of nuclear respiratory factor 1 and mitochondrial transcription factor A (markers of mitochondrial biogenesis), and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1 (markers of β-oxidation). HIIT improved all of these data in the C-HIIT and F-HIIT groups. In conclusion, in mice fed a fructose diet, HIIT improved body mass, blood pressure, glucose metabolism, and plasma triglycerides. Liver, WAT, and skeletal muscle were positively modulated by HIIT, indicating HIIT as a coadjutant treatment for diseases affecting these tissues.
NEW & NOTEWORTHY We investigated the effects of high-intensity interval training (HIIT) in mice fed a fructose-rich diet and the resulting severe negative effect on the liver, white adipose tissue (WAT), and skeletal muscle, which reduced the expression of fibronectin type III domain containing 5 (FNDC5, irisin) and PGC1α and, consequently, affected markers of mitochondrial biogenesis and β-oxidation. Because HIIT may block these adverse effects in all of these three tissues, it might be suggested that it functions as a coadjutant treatment in combatting the alterations caused by high-fructose intake.
Resistance exercise (RE) volume is recognized as an important factor that stimulates muscle protein synthesis (MPS) and is considered, at least in part, to be involved in the mammalian target of rapamycin complex 1 (mTORC1)-associated signaling. However, the effects of relatively high-volume RE on mTORC1 and MPS remain unclear. In the present study, we used an animal model of RE to investigate the relationship between RE volume and MPS. Male Sprague-Dawley rats were subjected to RE, and muscle samples were obtained 6 h after performing 1, 3, 5, 10, or 20 sets of RE. Although 1 set of RE did not increase MPS [measured by the surface sensing of translation (SUnSET) method], multiple sets (3, 5, 10, and 20 sets) significantly increased MPS. However, the increase in MPS reached a plateau after 3 or 5 sets of RE, and no further increase in MPS was observed with additional RE sets. In contrast to the MPS response, we observed that p70S6K phosphorylation at Thr389, a marker of mTORC1 activity, and Ser240/244 phosphorylation of rpS6, a downstream target of p70S6K, gradually increased with higher RE volume. The above results suggest that the relationship between RE volume and MPS was not linear. Thus the increase in MPS with increasing RE volume saturates before p70S6K phosphorylation, suggesting a threshold effect for the relationship between p70S6K activation and MPS.
NEW & NOTEWORTHY The aim of this study was to investigate the relationship between resistance exercise (RE) volume and muscle protein synthesis. We found that the relationship between RE volume and p70S6K phosphorylation was almost linear, but the increase in muscle protein synthesis began to plateau after approximately five sets of RE.
Exercise training is advocated for treating chronic inflammation and obesity-related metabolic syndromes. Glucocorticoids (GCs), the anti-inflammatory hormones, are synthesized or metabolized in extra-adrenal organs. This study aims to examine whether exercise training affects obesity-associated pulmonary inflammation by regulating local GC synthesis or metabolism. We found that sedentary obese (ob/ob) mice exhibited increased levels of interleukin (IL)-1β, IL-18, monocyte chemotactic protein (MCP)-1, and leukocyte infiltration in lung tissues compared with lean mice, which was alleviated by 6 wk of exercise training. Pulmonary corticosterone levels were decreased in ob/ob mice. Exercise training increased pulmonary corticosterone levels in both lean and ob/ob mice. Pulmonary corticosterone levels were negatively correlated with IL-1β, IL-18, and MCP-1. Immunohistochemical staining of the adult mouse lung sections revealed positive immunoreactivities for the steroidogenic acute regulatory protein, the cholesterol side-chain cleavage enzyme (CYP11A1), the steroid 21-hydroxylase (CYP21), 3β-hydroxysteroid dehydrogenase (3β-HSD), and type 1 and type 2 11β-hydroxysteroid dehydrogenase (11β-HSD) but not for 11β-hydroxylase (CYP11B1). Exercise training significantly increased pulmonary 11β-HSD1 expression in both lean and ob/ob mice. In contrast, exercise training per se had no effect on pulmonary 11β-HSD2 expression, although pulmonary 11β-HSD2 levels in ob/ob mice were significantly higher than in lean mice. RU486, a glucocorticoid receptor antagonist, blocked the anti-inflammatory effects of exercise training in lung tissues of obese mice and increased inflammatory cytokines in lean exercised mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local GC activation and suppression of pulmonary inflammation in obese mice.
NEW & NOTEWORTHY Treadmill training leads to a significant increase in pulmonary corticosterone levels in ob/ob mice, which is in parallel with the favorable effects of exercise on obesity-associated pulmonary inflammation. Exercise training increases pulmonary 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression but has no significant effect on 11β-HSD2 expression in both lean and ob/ob mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local glucocorticoid activation and suppression of pulmonary inflammation in obese mice.
Elevating core temperature at rest causes increases in minute ventilation (VE), which leads to reductions in both arterial CO2 partial pressure (hypocapnia) and cerebral blood flow. We tested the hypothesis that in resting heated humans this hypocapnia diminishes the ventilatory sensitivity to rising core temperature but does not explain a large portion of the decrease in cerebral blood flow. Fourteen healthy men were passively heated using hot-water immersion (41°C) combined with a water-perfused suit, which caused esophageal temperature (Tes) to reach 39°C. During heating in two separate trials, end-tidal CO2 partial pressure decreased from the level before heating (39.4±2.0 mmHg) to the end of heating (30.5±6.3 mmHg) (P=0.005) in the Control trial. This decrease was prevented by breathing CO2-enriched air throughout the heating such that end-tidal CO2 partial pressure did not differ between the beginning (39.8±1.5 mmHg) and end (40.9±2.7 mmHg) of heating (P=1.00). The sensitivity of VE to rising Tes (i.e., slope of the Tes-VE relation) did not differ between the Control and CO2-breathing trials (37.1±43.1 vs. 16.5±11.1 l·min-1·°C-1, P=0.31). In both trials, middle cerebral artery blood velocity (MCAV) decreased early during heating (all P<0.01), despite the absence of hyperventilation-induced hypocapnia. CO2-breathing increased MCAV relative to Control at the end of heating (P=0.005) and explained 36.6% of the heat-induced reduction in MCAV. These results indicate that during passive heating at rest, ventilatory sensitivity to rising core temperature is not suppressed by hypocapnia, and that most of the decrease in cerebral blood flow occurs independently of hypocapnia.
Blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) increases in healthy humans breathing hypoxic gas, and is potentially dependent on body position. Previous work in subjects breathing room air has shown an effect of body position when QIPAVA was detected using transthoracic saline contrast echocardiography (TTSCE). However, the potential effect of body position on QIPAVA has neither been investigated when breathing hypoxic gas, nor using a technique capable of quantifying QIPAVA. Thus, the purpose of this study was to quantify the effect of body position on QIPAVA when breathing normoxic and hypoxic gas at rest. We studied QIPAVA using TTSCE and quantified QIPAVA using filtered Technetium-99m-labeled macroaggregates of albumin (99mTc-MAA) in 7 healthy men breathing normoxic and hypoxic gas (12% O2) at rest, while supine and upright. Based on previous work using TTSCE, we hypothesized that the quantified QIPAVA would be greatest with hypoxia in the supine position. We found QIPAVA quantified with 99mTc-MAA to significantly increase while breathing hypoxic gas in both supine and upright body positions (QIPAVA = 0.7 ± 0.4 vs. 2.5 ± 1.1% of cardiac output, respectively). QIPAVA detected with TTSCE increased from normoxia in supine hypoxia, but not in upright hypoxia (median hypoxia bubble score of 2 vs 0, respectively). Surprisingly, QIPAVA magnitude was greatest in upright hypoxia when QIPAVA was undetectable with TTSCE. These findings suggest the relationship between TTSCE and 99mTc-MAA is more complex than previously appreciated perhaps because of the different physical properties of bubbles and MAA in solution.
Habitual aerobic exercise attenuates elevated vasoconstriction during acute exercise (functional sympatholysis) in older men; however, this effect remains unknown in postmenopausal women (PMW). This study tested the hypothesis that, PMW who participate in habitual aerobic exercise, demonstrate a greater functional sympatholysis compared to their untrained counterparts. Nineteen PMW (untrained, n=9 vs. trained, n=10) performed 5-minutes of steady-state (SS) forearm exercise at relative (10% and 20% of maximum; MVC) and absolute (5 kg) contraction intensities. Lower body negative pressure (LBNP) was used to increase sympathetic vasoconstriction during rest and forearm exercise. Brachial artery diameter and blood velocities (via Doppler ultrasound) determined forearm blood flow (FBF; ml·min-1). Forearm muscle oxygen consumption (VO2m; ml·min-1) and arterio-venous oxygen difference (a-vo2diff) were estimated during SS-exercise and SS-exercise with LBNP. Forearm vascular conductance (FVC; ml·min-1·100mmHg-1) was calculated from FBF and mean arterial pressure (MAP; mmHg). Vasoconstrictor responsiveness was determined as the % change in FVC during LBNP. The reduction in FVC (% change FVC) during LBNP was lower in trained compared to untrained PMW at 10% MVC (-7.3±1.2% vs. -13.0±1.1%; P<0.05), 20% MVC (-4.4±0.8% vs. -8.6±1.4%; P<0.05) and 5kg (-5.3±0.8% vs. -8.9±1.4%; P<0.05) conditions, whereas there were no differences at rest (-32.7±4.4% vs. -33.7±4.0%). Peripheral (FVC, FBF and VO2m) and the magnitude change in systemic hemodynamics (heart rate and MAP) did not differ between groups during exercise. Collectively, the findings present first evidence suggesting that PMW who participate in aerobic exercise demonstrate a greater functional sympatholysis compared to untrained PMW during mild-to-moderate forearm exercise.
Here we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia and for exercise capacity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8-10-month Tgαq*44 mice showed impaired systolic performance, reduced voluntary wheel running, but exhibit preserved inotropic reserve. At 12 month Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed increase in concentration of angiotensin-(1-7) in 6-10-month-old Tgαq*44 mice. However, at 12-14-month-old Tgαq*44 mice, increase angiotensin-II was noted with a concomitant increase in Ang III, IV, angiotensin A and angiotensin-(1-10). The pattern of changes in the heart and in the aorta was also compatible with activation of ACE-2 followed by activation of ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1-7) activation, possibly allowing to delay decompensation.
Resistance exercise during the postprandial period lowers venous glucose concentrations in individuals with type 2 diabetes, but the impact of resistance exercise on interstitial glucose concentrations is not well understood. The objective of this study was to compare subcutaneous adipose tissue interstitial glucose and venous blood glucose concentrations during postprandial resistance exercise in patients with type 2 diabetes. Eleven individuals completed two trials in a random order including a no exercise (NoEx) and a postprandial resistance exercise trial (M-Ex). During the trials the individuals consumed a meal and either remained sedentary (NoEx) or performed a session of resistance training beginning 45 min after the meal (M-Ex) while interstitial and venous glucose concentrations were simultaneously measured. Venous glucose during exercise was ~11% lower (P=0.05) during M-Ex (8.0±0.5 mmol/L) compared to NoEx (9.0±0.5 mmol/L) whereas interstitial glucose during M-Ex (10.4±0.7 mmol/L) was not different compared to interstitial glucose during NoEx (10.1±0.7 mmol/L). Bland-Altman plots revealed that the difference (bias) between interstitial and venous glucose during exercise was over 2-fold greater during M-Ex (2.36±2.07 mmol/L) compared to NoEx (1.11±1.69 mmol/L). The mean (33.8±6.2 mmol/L) and median (34.7±6.3 mmol/L) absolute relative difference during exercise were 73% and 78% greater compared to the mean (19.5±4.1 mmol/L) and median (19.5±4.1 mmol/L) absolute relative difference during NoEx (P=0.04). Resistance exercise has unequal effects on glucose concentrations within different bodily compartments as exercise reduced venous glucose concentrations but not adipose tissue interstitial glucose concentrations in the abdominal region in individuals with type 2 diabetes.
Wearable sensors allow continuous monitoring of metabolites for diabetes, sports medicine, exercise science, and physiology research. These sensors can continuously detect target analytes in skin interstitial fluid (ISF), tears, saliva, and sweat. In this review, we will summarize developments on wearable devices and their potential applications in research, clinical practice, and recreational and sporting activities. Sampling skin ISF can require insertion of a needle into the skin, whereas sweat, tears, and saliva can be sampled by devices worn outside the body. The most widely sampled metabolite from a wearable device is glucose in skin ISF for monitoring diabetes patients. Continuous ISF glucose monitoring allows estimation of the glucose concentration in blood without the pain, inconvenience, and blood waste of fingerstick capillary blood glucose testing. This tool is currently used by diabetes patients to provide information for dosing insulin and determining a diet and exercise plan. Similar technologies for measuring concentrations of other analytes in skin ISF could be used to monitor athletes, emergency responders, warfighters, and others in states of extreme physiologic stress. Sweat is a potentially useful substrate for sampling analytes for metabolic monitoring during exercise. Lactate, sodium, potassium, and hydrogen ions can be measured in sweat. Tools for converting the concentrations of these analytes sampled from sweat, tears, and saliva into blood concentrations are being developed. As an understanding of the relationships between the concentrations of analytes in blood and easily sampled body fluids increases, then the benefits of new wearable devices for metabolic monitoring will also increase.
Black adults have a higher risk of hypertension compared to non-Hispanic white (NHW) adults, but physiological mechanisms underlying this predisposition remain unclear. This study compared muscle sympathetic nerve activity (MSNA) responses to mental stress in a group of young black and NHW participants. We hypothesized that the sympathoexcitation associated with mental stress would be greater in black adults compared to NHW. Thirty-five male adults (19 black, 23±1 years; 16 NHW, 22±1 years) were examined during a 5 min supine baseline and 5 min of mental stress (via mental arithmetic). Baseline mean arterial pressure (80±2 vs. 82±1 mmHg), heart rate (61±4 vs. 61±2 beats/min), MSNA (13±1 vs. 15±2 bursts/min), and sympathetic baroreflex sensitivity (-1.1 ± 0.4 vs -1.5 ± 0.3 bursts/100hb/mmHg) were not significantly different between NHW and black adults (p>0.05), respectively. MSNA reactivity to mental stress was significantly higher in NHW compared to black adults (time x race, p=0.006), with a particularly divergent responsiveness during the first minute of mental stress in NHW (4±1 burst/min) and black (-2±2 burst/min; p = 0.022). Blood pressure and heart rate reactivity to mental stress was similar between groups. In summary, black participants demonstrated a lower MSNA responsiveness to mental stress compared to NHW adults. These findings suggest that despite a higher prevalence of hypertension, blacks do not appear to have higher neural and cardiovascular responsiveness to mental stress when compared to NHW.
Numerous situations, such as the recovery from illness or rehabilitation after injury, necessitate a period of muscle disuse in otherwise healthy individuals. Even a few days of immobilization or bed rest can lead to substantial loss of skeletal muscle tissue and compromises metabolic health. The decline in muscle mass is largely attributed to a decline in postabsorptive and postprandial muscle protein synthesis rates. Re-introduction of some level of muscle contraction by the application of neuromuscular electrical stimulation (NMES) can augment both postabsorptive and postprandial muscle protein synthesis rates and, as such, prevent or attenuate muscle loss during short-term disuse in various clinical populations. Whereas maintenance of habitual dietary protein consumption is a prerequisite for muscle mass maintenance, supplementing dietary protein above habitual intake levels does not prevent muscle loss during disuse in otherwise healthy humans. Combining the anabolic properties of physical activity (or surrogates) with appropriate nutritional support likely further increases the capacity to preserve skeletal muscle mass during a period of disuse. Therefore, effective interventional strategies to prevent or alleviate muscle disuse atrophy should include both exercise (mimetics) and appropriate nutritional support.
Porcine respiratory and reproductive syndrome (PRRS), caused by PRRS virus (PRRSV), is one of the most serious infectious diseases in the swine industry worldwide. Indigenous Chinese Tongcheng (TC) pigs reportedly show strong resistance to PRRSV infection. The miRNA expression profiles of porcine alveolar macrophages (PAMs) of control TC pigs and those infected with PRRSV in vivo were analyzed by high-throughput sequencing to explore changes induced by infection. A total of 182 known miRNAs including 101 miRNA-5p and 81 miRNA-3p were identified with 23 up-regulated differentially expressed miRNAs (DEmiRNAs) and 25 down-regulated DEmiRNAs. Gene Ontology analysis showed that predicted target genes for the DEmiRNAs were enriched in immune response, transcription regulation, and cell death. The integrative analysis of mRNA and miRNA expression revealed that down-regulated methylation-related genes (DNMT1 and DNMT3b) were targeted by five up-regulated DEmiRNAs. Furthermore, 35 pairs of miRNAs (70 miRNAs) were co-expressed after PRRSV infection and six pairs were co-expressed differently. Our results describe miRNA expression profiles of TC pigs in response to PRRSV infection and lay a strong foundation for developing novel therapies to control PRRS in pigs.