Protective Role of Interleukin-10 in Ozone-Induced Pulmonary Inflammation

BackgroundThe mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators.ObjectivesWe investigated the molecular mechanisms underlying interleuken-10 (IL-10)–mediated attenuation of O3-induced pulmonary inflammation in mice.MethodsIl10-deficient (Il10−/−) and wild-type (Il10+/+) mice were exposed to 0.3 ppm O3 or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation.ResultsMean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10−/− mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10−/− compared with Il10+/+ mice. Gene expression analyses revealed several IL-10–dependent and O3-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3.ConclusionsResults indicate that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals

STZ-induced skeletal muscle atrophy is associated with increased p65 content and downregulation of insulin pathway without NF-κB canonical cascade activation

Type 1 diabetes mellitus (DM)-induced skeletal muscle atrophy is associated with an increased incidence in morbidity and mortality. Although the precise mechanism of diabetes-induced skeletal muscle atrophy remains to be established, several NF-κB-dependent pro-inflammatory genes have been identified as potential therapeutic targets. Moreover, activation of NF-κB has previously been shown to be required for cytokine-induced loss of skeletal muscle proteins. Therefore, we investigated activation of the NF-κB canonical pathway, concomitant to insulin signaling activation in skeletal muscle from diabetes-induced rats. Ten rats injected with streptozotocin (STZ) 4 weeks prior to tissue extraction were compared to 10 control rats. Using total, cytosolic and nuclear protein extracts from hindlimb muscles: soleus (SOL), extensor digitorum longus (EDL), gastrocnemius (GM) and liver tissue, we assessed key proteins important for the activation of both NF-κB and insulin pathways. Insulin blood concentration decreased to 3.9 ± 1.2 mU/ml following STZ-injection resulting in hyperglycemia (17.9 ± 0.7 mmol/l). SOL, EDL and GM mass decreased, and liver mass increased following STZ injection. NF-κB/p65 content in SOL, GM and liver increased in STZ-injected rats, without any change in IκB degradation or IKK phosphorylation. Muscle NF-κB/p65 remained bound to IκB and did not translocate or bind to DNA. Although the canonical NF-κB cascade was not activated, STZ induced a decrease in insulin pathway proteins including insulin receptor (IR) and substrate (IRS-1) content and phosphorylation compared to control animals. A downregulation of insulin pathway proteins and muscle atrophy occurred in response to STZ administration, and despite increased p65 content, STZ treatment did not activate the canonical NF-κB cascade. Therefore, it is unlikely that hyperglycemia initiates skeletal muscle atrophy via activation of the NF-κB canonical pathway

Satiety, but not total PYY, Is increased with continuous and intermittent exercise

Objective This study determined the hormonal and subjective appetite responses to exercise (1-h continuous versus intermittent exercise throughout the day) in obese individuals. Design and Methods Eleven obese subjects (>30 kg/m2) underwent three 12-h study days: control condition [sedentary behavior (SED)], continuous exercise condition [(EX) 1-h exercise], and intermittent exercise condition [(INT) 12 hourly, 5-min bouts]. Blood samples (every 10 min) were measured for serum insulin and total peptide YY (PYY) concentrations, with ratings of appetite (visual analog scale [VAS): every 20 min]. Both total area under the curve (AUC), and subjective appetite ratings were calculated. Results No differences were observed in total PYY AUC between conditions, but hunger was reduced with INT (INT EX and SED > EX; P < 0.05). A correlation existed between the change in total PYY and insulin levels (r = −0.81; P < 0.05), and total PYY and satiety (r = 0.80; P < 0.05) with the EX condition, not the SED and INT conditions. Conclusions The total PYY response to meals is not altered over the course of a 12-h day with either intermittent or continuous exercise; however, intermittent exercise increased satiety and reduced hunger to a greater extent than continuous exercise in obese individuals

Multiple short bouts of exercise over 12-h period reduce glucose excursions more than an energy-matched single bout of exercise

Objective Long, uninterrupted bouts of sedentary behavior are thought to negatively influence postprandial glucose and insulin concentrations. We examined the effects of a 1-h bout of morning exercise versus intermittent walking bouts of short duration on glucose excursions and insulin secretion over 12-h. Materials/Methods Eleven young, obese individuals (18–35 years, BMI > 30 kg/m2) with impaired glucose tolerance were studied on three 12-h study days: 1) sedentary behavior (SED); 2) sedentary behavior with 1-h morning exercise (EX) at 60%–65% VO2peak; and 3) sedentary behavior with 12-hourly, 5-min intervals of exercise (INT) at 60%–65% VO2peak. Meals (1046 kJ/meal) were provided every 2-h. Blood samples were collected every 10 min and measured for glucose, insulin, and c-peptide concentrations. Results Glucose iAUC (12-h) was attenuated in the INT and SED conditions compared to the EX condition (P < 0.05). Glucose concentrations were higher in the EX compared to the SED condition for ~ 150 min (20% of the study day), and comparison of the EX-INT study days revealed that glucose concentrations were greater for ~ 240 min (~ 1/3 of the 12-h day). In the SED condition, the 12-h insulin iAUC was ~ 15% higher (P < 0.05) compared to the INT and EX conditions. Insulin production rate was found to increase ~ 20% with INT exercise vs. the SED and EX condition (P < 0.05). Conclusions Short, frequent periods of exercise attenuated glucose excursions and insulin concentrations in obese individuals to a greater degree than an equal amount of exercise performed continuously in the morning

Effect of increased physical activity on fructose-induced glycemic response in healthy individuals

Background/Objectives: The purpose of the current study was to determine whether increased physical activity (PA) altered glycemic control while ingesting an energy-balanced high-fructose diet. Subjects/Methods: Twenty-two normal-weight men and women (age: 21.2±0.6 years; body mass index: 22.6 ±0.6 kg/m2) participated in a randomized, cross-over design study in which they ingested an additional 75 g of fructose for 14 days while either maintaining low PA (FR+inactive) (12 000 steps/day). Before and following the 2-week loading period, a fructose-rich meal challenge was administered and blood was sampled at baseline and for 6 h after the meal and analyzed for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), c-peptide, glucose and insulin concentrations. Results: Plasma insulin, glucose, c-peptide, GIP and GLP-1 concentrations significantly increased in response to the test meal on all test visits (P<0.05). C-peptide incremental area under the curve (AUC) decreased by 10 208 ±120 pmol/l × min for 6 h from pre to post Fr+active intervention (P=0.02) leading to a decrease in plasma insulin total AUC (pre: 58 470.2±6261.0 pmol/l; post: 49 444.3±3883.0 pmol/l; P=0.04) resulting in a decrease Δpeak[Insulin] (P=0.009). Following the FR+active intervention, GIP total AUC significantly decreased (P=0.005) yet only males had a lower total GLP-1 AUC after both interventions (P=0.049). There were no sex differences in GIP levels. Conclusions: Increased PA attenuates the deleterious effects on glycemic control caused by a high-fructose diet. These changes in glycemic control with PA are associated with decreases in insulin and GIP concentrations

Effect of Bisphenol A (BPA) on Skeletal Muscle Oxidative Stress

Receno, C., Benson, M., Liang, C., Keslacy, S., DeRuisseau, K. Syracuse University, Syracuse, NY Purpose: Bisphenol A (BPA) is a chemical used in many plastics and food-contact materials that has been linked to several health conditions, including type II diabetes. BPA is classified as an “endocrine disruptor” for its potential to exert estrogen-like activity and has been linked to the development of oxidative stress. BPA exposure may be particularly important to skeletal muscle since changes in redox status can have large implications for contractile and metabolic properties. Therefore, the aim of this study was to determine the impact of BPA exposure on indices of oxidative stress in skeletal muscle. Methods: Mouse myoblast C2C12 cells were cultured and exposed to BPA or a 0.1% ethanol vehicle. The BPA concentrations examined included 1nM, 10nM or 100nM for incubation times of 24 hours, 6 hours, 40 minutes or 15 minutes. Triplicate samples within each experiment were pooled, and each experiment was conducted three times. Using the Western Blot technique, samples were analyzed for oxidant levels using 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) antibodies as well as key antioxidant enzymes; superoxide dismutase-1 (SOD1) and glutathione peroxidase (GPX). Data were analyzed via 2-way or 1-way ANOVAs with SPSS v21. Results: No significant differences were detected in dose/exposure groups for oxidant levels (3-NT and 4-HNE) or GPX. However, at 24 hours, 100 nM BPA resulted in greater SOD1 (11.28+2.8 fold change, pConclusion:BPA exposure for 24 hours at 100nM concentration elevated SOD1 levels compared to all other time points and doses but did not increase markers of oxidant injury. These data suggests that chronic long term BPA exposure could alter the skeletal muscle antioxidant status. Research funded by Syracuse University, School of Education

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise.

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P &lt; 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P &lt; 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P &lt; 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise

The metabolic costs of reciprocal supersets vs. traditional resistance exercise in young recreationally active adults

An acute bout of traditional resistance training (TRAD) increases energy expenditure (EE) both during exercise and in the postexercise period. Reciprocal supersets (SUPERs) are a method of resistance training that alternates multiple sets of high-intensity agonist-antagonist muscle groups with limited recovery. The purpose of this study was to compare the energy cost of SUPERs and TRAD both during and in the postexercise period. We hypothesized that SUPERs would produce greater exercise EE relative to the duration of exercise time and greater excess postexercise oxygen consumption (EPOC) than TRAD of matched work. Ten recreationally active, young men each participated in 2 exercise protocols: SUPER, followed 1 week later by TRAD matched within using a 10-repetition maximum load for 6 exercises, 4 sets, and repetitions. Participants were measured for oxygen consumption and blood lactate concentration during exercise and 60 minutes postexercise after each exercise bout. No significant differences were observed in aerobic exercise EE between trials (SUPER 1,009.99 ± 71.42 kJ; TRAD 954.49 ± 83.31 kJ); however, when expressed relative to time, the exercise EE was significantly greater during SUPER (34.70 ± 2.97 kJ·min-1) than TRAD (26.28 ± 2.43 kJ·min-1). Excess postexercise oxygen consumption was significantly greater after SUPER (79.36 ± 7.49 kJ) over TRAD (59.67 ± 8.37 kJ). Average blood lactate measures were significantly greater during SUPER (5.1 ± 0.9 mmol·L-1) than during TRAD (3.8 ± 0.6 mmol·L-1). Reciprocal supersets produced greater exercise kJ·min-1, blood lactate, and EPOC than did TRAD. Incorporating this method of resistance exercise may benefit exercisers attempting to increase EE and have a fixed exercise volume with limited exercise time available

Physical activity offsets the negative effects of a High-Fructose diet

Objective: This study aimed to determine the interaction between a high-fructose diet and PA levels on postprandial lipidemia and inflammation in normal-weight, recreationally active individuals. Methods: Twenty-two men and women (age, 21.2 ± 0.6 yr; body mass index, 22.5 ± 0.6 kg•m−2) consumed an additional 75 g of fructose for 14 d on two separate occasions: high physical activity (PA) (approximately 12,500 steps per day) (FR+active) and low PA (approximately 4500 steps per day) (FR+inactive). A fructose-rich test meal was given before and at the end of each intervention. Blood was sampled at baseline and for 6 h after the meal for triglycerides (TG), VLDL, total cholesterol, glucose, insulin, tumor necrosis factor-α, interleukin 6, and C-reactive protein. Results: Log-transformed TG area under the curve (AUC) significantly increased from before (10.1 ± 0.1 mg•dL−1 × min for 6 h) to after (10.3 ± 0.08 mg•dL−1 × min for 6 h, P = 0.04) the FR+inactive intervention, with an 88% increase in Δpeak TG (P = 0.009) and an 84% increase in Δpeak VLDL (P = 0.002). ΔPeak interleukin 6 also increased by 116% after the FR+inactive intervention (P = 0.009). Insulin total AUC significantly decreased after FR+active intervention (P = 0.04), with no change in AUC after the FR+inactive intervention. No changes were observed in glucose, tumor necrosis factor-α, and C-reactive protein concentrations (P > 0.05). Conclusions: Low PA during a period of high fructose intake augments fructose-induced postprandial lipidemia and inflammation, whereas high PA minimizes these fructose-induced metabolic disturbances. Even within a young healthy population, maintenance of high PA (>12,500 steps per day) decreases susceptibility to cardiovascular risk factors associated with elevated fructose consumption

Addition of inspiratory resistance increases the amplitude of the slow component of O2 uptake kinetics.

The contribution of respiratory muscle work to the development of the O(2) consumption (Vo(2)) slow component is a point of controversy because it has been shown that the increased ventilation in hypoxia is not associated with a concomitant increase in Vo(2) slow component. The first purpose of this study was thus to test the hypothesis of a direct relationship between respiratory muscle work and Vo(2) slow component by manipulating inspiratory resistance. Because the conditions for a Vo(2) slow component specific to respiratory muscle can be reached during intense exercise, the second purpose was to determine whether respiratory muscles behave like limb muscles during heavy exercise. Ten trained subjects performed two 8-min constant-load heavy cycling exercises with and without a threshold valve in random order. Vo(2) was measured breath by breath by using a fast gas exchange analyzer, and the Vo(2) response was modeled after removal of the cardiodynamic phase by using two monoexponential functions. As anticipated, when total work was slightly increased with loaded inspiratory resistance, slight increases in base Vo(2), the primary phase amplitude, and peak Vo(2) were noted (14.2%, P &lt; 0.01; 3.5%, P &gt; 0.05; and 8.3%, P &lt; 0.01, respectively). The bootstrap method revealed small coefficients of variation for the model parameter, including the slow-component amplitude and delay (15 and 19%, respectively), indicating an accurate determination for this critical parameter. The amplitude of the Vo(2) slow component displayed a 27% increase from 8.1 +/- 3.6 to 10.3 +/- 3.4 ml. min(-1). kg(-1) (P &lt; 0.01) with the addition of inspiratory resistance. Taken together, this increase and the lack of any differences in minute volume and ventilatory parameters between the two experimental conditions suggest the occurrence of a Vo(2) slow component specific to the respiratory muscles in loaded condition