Autophagy of naïve CD4+ T cells in aging - the role of body adiposity and physical fitness.

Life expectancy has increased exponentially in the last century accompanied by disability, poor quality of life, and all-cause mortality in older age due to the high prevalence of obesity and physical inactivity in older people. Biologically, the aging process reduces the cell's metabolic and functional efficiency, and disrupts the cell's anabolic and catabolic homeostasis, predisposing older people to many dysfunctional conditions such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. In the immune system, aging also alters cells' metabolic and functional efficiency, a process known as 'immunosenescence', where cells become more broadly inflammatory and their functionality is altered. Notably, autophagy, the conserved and important cellular process that maintains the cell's efficiency and functional homeostasis may protect the immune system from age-associated dysfunctional changes by regulating cell death in activated CD4+ T cells. This regulatory process increases the delivery of the dysfunctional cytoplasmic material to lysosomal degradation while increasing cytokine production, proliferation, and differentiation of CD4+ T cell-mediated immune responses. Poor proliferation and diminished responsiveness to cytokines appear to be ubiquitous features of aged T cells and may explain the delayed peak in T cell expansion and cytotoxic activity commonly observed in the 'immunosenescence' phenotype in the elderly. On the other hand, physical exercise stimulates the expression of crucial nutrient sensors and inhibits the mechanistic target of the rapamycin (mTOR) signaling cascade which increases autophagic activity in cells. Therefore, in this perspective review, we will first contextualize the overall view of the autophagy process and then, we will discuss how body adiposity and physical fitness may counteract autophagy in naïve CD4+ T cells in aging.

Exercise training induces alteration of clock genes and myokines expression in tumor-bearing mice.

To investigate the impact of different exercise training schedules (following a fixed schedule or at random times of the day) on clock genes and myokine expression patterns in the skeletal muscle of tumor-bearing mice. Mice were divided into three groups: tumor (LLC), tumor + exercise training (LLC + T) always performed at the same time of the day (ZT2) and exercise training at random times of the day (ZTAlt). Mice were inoculated subcutaneously with Lewis lung carcinoma cells. The gastrocnemius muscle was dissected and the clock gene expression (Clock/Per1/Per2/Per3/Rev-Erbα/GAPDH) was investigated by quantitative reverse transcription polymerase chain reaction with SYBR® Green. Myokine content in muscle (tumour necrosis factor alpha/IL-10/IL-4) was assessed by enzyme-linked immunosorbent assay. At the end of the protocol, the trained groups showed a reduction in total weight, when compared to Lewis lung carcinoma. Tumor weight was lower in the LLC + T (ZTAlt), when compared to LLC. Clock gene mRNA expression showed a significant increase for ZT20 in the groups that performed physical exercise at LLC + T (ZTAlt), when compared with LLC. The Per family showed increased mRNA expression in ZT4 in both trained mice groups, when compared with LLC. LLC + T (ZTAlt) presented reduction of the expression of anti-inflammatory myokines (Il-10/IL-4) during the night, compared with LLC + T(ZT2). Exercise training is able to induce marked modification of clock gene expression and of the production of myokines, in a way that is dependent on schedule exercise training strategy. Taken together, the results show that exercise is a potent Zeitgeber and may thus contribute to change clock genes expression and myokines that are able to reduce the tumor weight.

High-intensity intermittent exercise induces a potential anti-inflammatory response in healthy women across the menstrual cycle.

AIM: This observational study aimed to examine cytokine responses to high-intensity intermittent exercise (HIIE) in the follicular and luteal phases of the menstrual cycle. METHODS: Fourteen healthy women (24 ± 2 years; body mass index [BMI]: 22.8 ± 1.9 kg⋅m2; maximal oxygen consumption [V̇O2max]: 41.5 ± 4.1 mL⋅kg-1⋅min-1) with regular menstrual cycles were randomly assigned to 4 experimental sessions, 2 during the follicular and 2 during the luteal phase. V̇O2max and maximum aerobic velocity (MAV) were determined prior to the experimental sessions through a graded exercise test during both follicular and luteal phases. Seventy-two hours after having completed the graded exercise test, all participants performed a HIIE session (10 x 1-min sprints with 1 min of rest) at 90% of their MAV. Serum concentrations of TNF-α, IL-6, IL-10 and IL-17 were measured before (Pre), immediately after (Post) and 1 h after (1 h Post) the HIIE sessions. RESULTS: Pre-exercise concentrations of TNF-α and IL-10 were significantly higher in the luteal phase compared to the follicular phase (P < 0.01), with no differences seen on IL-6 and IL-17, demonstrating an altered inflammatory status in the luteal phase. There was a significant interaction for IL-10 concentration (P < 0.01) with reductions in both luteal (Pre vs Post, 95 %CI: 1.086 to 6.156; and Pre vs 1 h Post, 95 %CI: 1.720 to 9.013, P < 0.01) and follicular phase (Pre vs 1 h Post, 95 %CI: 0.502 to 7.842, P < 0.05). Despite no significant phase × time interaction for TNF-α concentration, its concentration at 1 h Post was significantly lower compared to Pre in the luteal phase analysis (Pre vs 1 h Post, 95 %CI: 0.71 to 14.06; P < 0.05). These results are in agreement with IL-10 responses, highlighting a reduction on the inflammatory status after exercise. CONCLUSION: Mostly during the luteal phase, high-intensity intermittent exercise modulates cytokine responses, thus impacting exercise recovery. In this scenario, high-intensity intermittent exercise emerges as a non-pharmacology strategy to regulate inflammatory responses on healthy women who were affected by an inflammatory state given their menstrual cycle.

Immunometabolism-fit: How exercise and training can modify T cell and macrophage metabolism in health and disease.

BACKGROUND: The term immunometabolism describes cellular and molecular metabolic processes that control the immune system and the associated immune responses. Acute exercise and regular physical activity have a substantial influence on the metabolism and the immune system, so that both processes are closely associated and influence each other bidirectionally. SCOPE OF REVIEW: We limit the review here to focus on metabolic phenotypes and metabolic plasticity of T cells and macrophages to describe the complex role of acute exercise stress and regular physical activity on these cell types. The metabolic and immunological consequences of the social problem of inactivity and how, conversely, an active lifestyle can break this vicious circle, are then described. Finally, these aspects are evaluated against the background of an aging society. MAJOR CONCLUSIONS: T cells and macrophages show high sensitivity to changes in their metabolic environment, which indirectly or directly affects their central functions. Physical activity and sedentary behaviour have an important influence on metabolic status, thereby modifying immune cell phenotypes and influencing immunological plasticity. A detailed understanding of the interactions between acute and chronic physical activity, sedentary behaviour, and the metabolic status of immune cells, can help to target the dysregulated immune system of people who live in a much too inactive society.

Menstrual cycle impacts adipokine and lipoprotein responses to acute high-intensity intermittent exercise bout.

Due to hormonal fluctuation, the menstrual cycle impacts inflammatory response and lipid metabolism; moreover, the anti-atherogenic and anti-inflammatory effects of exercise in this cycle, mainly high-intensity intermittent exercise (HIIE), need to be examined. Therefore, the aim of the current study was to investigate the influence of menstrual cycle phases on adipokine and lipoprotein responses after acute HIIE sessions in healthy women. Fourteen women (age: 24 ± 2 years; BMI: 22.79 ± 1.89 kg·m2) were recruited to perform two HIIE sessions (10 × 1 min running at 90% of maximum aerobic velocity, with 1 min recovery); one during the follicular phase (FP) and other during the luteal phase (LP), randomly. Blood samples were collected at rest, immediately, and 60 min after HIIE sessions. Macrophage inflammatory protein-1α (MIP-1α), leptin, adiponectin, total cholesterol, triacylglycerol (TAG), HDL-c, and glucose concentrations were analyzed. At rest, higher MIP-1α concentrations were observed during the LP compared to FP (p = 0.017). Likewise, leptin (p = 0.050), LDL-c (p = 0.015), and non-HDL (p = 0.016) were statistically higher in the LP. In contrast, the adiponectin/leptin ratio was lower in the LP compared to the ratio found in the FP (p = 0.032). Immediately post-HIIE sessions, in both menstrual phases, higher TAG (p = 0.001) and HDL-c (p = 0.001) concentrations were found, which returned to resting levels after 60 min. In conclusion, adipokine and lipoprotein responses after a single HIIE session are regulated by the phase of the menstrual cycle, contributing to inflammatory conditions, and demonstrating the importance of considering the phases of the menstrual cycle for the periodization of physical training.

Acute Capsaicin Supplementation Improved Resistance Exercise Performance Performed After a High-Intensity Intermittent Running in Resistance-Trained Men.

ABSTRACT: de Freitas, MC, Cholewa, JM, Panissa, VLG, Toloi, GG, Netto, HC, Zanini de Freitas, C, Freire, RV, Lira, FS, and Rossi, FE. Acute capsaicin supplementation improved resistance exercise performance performed after a high-intensity intermittent running in resistance-trained men. J Strength Cond Res 36(1): 130-134, 2022-We sought to investigate the acute effects of capsaicin supplementation on the rate of perceived exertion (RPE) and heart rate during high-intensity intermittent exercise (HIIE) and resistance exercise performance executed after HIIE in resistance-trained men. Eleven resistance-trained men completed 2 randomized, double-blind trials: capsaicin condition or a placebo condition. The concurrent exercise session was composed of a 5-km intermittent run (1:1 effort and passive recovery ratio) and subsequent resistance exercise (4 × 70% of 1RM until muscle failure in the half-squat exercise). Heart rate was recorded during HIIE and after the protocol RPE (0-10 scale) was accessed. The resistance exercise performance was analyzed by the maximum number of repetitions performed for each set and the total volume (repetitions × weight lifted). During HIIE, the RPE (capsaicin = 7 ± 1 vs. placebo = 8 ± 1 points, t = -3.674, p = 0.005) and mean heart rate (capsaicin = 153 ± 13 vs. placebo = 158 ± 12 bpm, t = -2.292, p = 0.048) were significantly lower in the capsaicin compared with placebo condition. For subsequent resistance exercise, there was a significant decrease in volume across time (F = 19.889, p < 0.001, η2= 0.69) with maximal number of repetitions performed in capsaicin than placebo condition (2,077.6 ± 465.2 kg vs. 1,838.9 ± 624.1 kg, p = 0.028, d = 0.43), but the condition vs. set was not significant (F = 0.582, p = 0.632, η2= 0.06). Acute capsaicin supplementation induced a lower mean heart rate and RPE during HIIE and improved subsequent resistance exercise performance in resistance-trained men.

Inflammatory cytokines and metabolic responses to high-intensity intermittent training: effect of the exercise intensity.

To examine the effects of two high-intensity intermittent training (HIIT) programs of varying intensities (100% vs. 110% of maximal aerobic velocity [MAV]) on metabolic, hormonal and inflammatory markers in young men. Thirty-seven active male volunteers were randomly assigned into: HIIT experimental groups (100% MAV [EG100, n = 9] and 110% MAV [EG110, n = 9]) and a control groups (CG100, n = 9 and CG110, n = 9). Particpants performed high intesity intermittent exercise test (HIIE) at 100% or 110% MAV. Venous blood samples were obtained before, at the end of HIIE and at 15 min of recovery, and before and after 8 weeks of HIIT programs. After training, Glucose was lower (p < 0.01) in EG100 (d = 0.72) and EG110 (d = 1.20) at the end of HIIE, and at 15 min recovery only in EG110 (d = 0.95). After training, Insulin and Cortisol were lower than before training in EG100 and EG110 at the end of HIIE (p < 0.001). After HIIT, IL-6 deceased (p < 0.001) in EG100 (d = 1.43) and EG110 (d = 1.56) at rest, at the end of HIIE (d = 1.03; d = 1.75, respectively) and at 15 min of recovery (d = 0.88;d = 1.7, respectively). This decrease was more robust (p < 0.05) in EG110 compared to EG100. After HIIT, TNF-α deceased (p < 0.001) in EG100 (d = 1.43) and EG110 (d = 0.60) at rest, at the end of HIIE (0.71 < d < 0.98) and at 15 min of recovery (0.70 < d < 2.78). HIIT with 110% MAV is more effective in young males on the improvements of some metabolic (Glucose), hormonal (Cortisol) and inflammatory (IL-6) markers at rest, at the end of HIIE and 15 min of recovery than training at 100 % MAV.

Improvement in the anti-inflammatory profile with lifelong physical exercise is related to clock genes expression in effector-memory CD4+ T cells in master athletes.

PURPOSE: Ageing is associated with alterations in the immune system as well as with alterations of the circadian rhythm. Immune cells show rhythmicity in execution of their tasks. Chronic inflammation (inflammaging), which is observed in the elderly, is mitigated by lifelong exercise. The aimed this study was to determine the acute effect of a maximal exercise test on clock genes, regulatory proteins and cytokine expression, and evaluate the effect of lifelong exercise on the expression of clock genes in subpopulations of effector-memory (EM) CD4+ and CD8+T cells and the association of these processes with the inflammatory profile. Therefore, this study aimed to investigate the expression of clock genes in subpopulations of effector memory (EM) CD4+ and CD8+ T cells in master athletes and healthy controls and further associate them with systemic inflammatory responses to acute exercise. METHODS: The study population comprised national and international master athletes (n = 18) involved in three sports (athletics, swimming and judo). The control group (n = 8) comprised untrained healthy volunteers who had not participated in any regular and competitive physical exercise in the past 20 years. Anthropometric measurements and blood samples were taken before (Pre), 10 min after (Post) and 1 h after (1 h Post) a maximal cycle ergometer test for the determination of maximum oxygen consumption (VO2 max). The subpopulations of EM CD4+ and CD8+ T cells were purified using fluorescenceactivated cell sorting. RNA extraction of clock genes (CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBα, REV-ERBß, RORa, RORb and RORc) in EM CD4+ and EM CD8+ T cells as well as regulatory proteins (IL-4, IFN-γ, Tbx21, PD-1, Ki67, NF-kB, p53 and p21) in EM CD4+ T cells was performed. The serum concentration of cytokines (IL-8, IL-10, IL-12p70 and IL-17A) was measured. RESULTS: The master athletes showed better physiological parameters than the untrained healthy controls (P < 0.05). The levels of cytokines increased in master athletes at Post compared with those at Pre. The IL-8 level was higher at 1 h Post, whereas the IL-10 and IL-12p70 levels returned to baseline. There was no change in IL-17A levels (P < 0.05). The clock genes were modulated differently in CD4+ T cells after an acute session of exercise in a training status-dependent manner. CONCLUSION: The synchronization of clock genes, immune function and ageing presents new dimensions with interesting challenges. Lifelong athletes showed modified expression patterns of clock genes and cytokine production associated with the physical fitness level. Moreover, the acute bout of exercise altered the clock machinery mainly in CD4+ T cells; however, the clock gene expressions induced by acute exercise were different between the master athletes and control group.

Postactivation Potentiation Improves Acute Resistance Exercise Performance and Muscular Force in Trained Men.

ABSTRACT: Conrado de Freitas, M, Rossi, FE, Colognesi, LA, de Oliveira, JVNS, Zanchi, NE, Lira, FS, Cholewa, JM, and Gobbo, LA. Postactivation potentiation improves acute resistance exercise performance and muscular force in trained men. J Strength Cond Res 35(5): 1357-1363, 2021-The purpose of this study was to investigate the effects of heavy back squat (90% one repetition maximum [1RM]) postactivation potentiation (PAP) on acute resistance exercise performance and force production in recreationally trained men, and to verify the relationship between maximal strength and the PAP response. Ten resistance-trained men randomly completed 4 experimental trials: (a) back squats without PAP (No-PAP), (b) back squats with PAP, (c) maximum voluntary isometric contraction (MVIC) of the quadriceps without PAP, and (d) MVIC with PAP. Back squats were performed with 4 sets at 70% of 1 RM with 2 minutes of rest interval. The number of squats repetitions performed was recorded for each set, and a total number of repetitions were calculated to analyze performance. Maximum voluntary isometric contraction was measured using electronic dynamometer, and the peak force and mean force were recorded. Blood lactate concentration was analyzed presquat and postsquat exercise. Repetitions performed in the first set was significantly (p < 0.001) greater in the PAP condition (22.00 ± 5.14) compared with No-PAP (15.50 ± 5.10), which resulted in significantly (p = 0.001) more total repetitions performed in the PAP (56.20 ± 17.3) condition compared with No-PAP (48.80 ± 14.5). Maximum voluntary isometric contraction peak was higher in PAP than in No-PAP (PAP = 765.7 ± 147.8 vs. No-PAP = 696.8 ± 131.5 N, p = 0.006). No significant correlations were observed between back squat 1RM relative to body mass and the PAP response in squat and MVIC. There were no significant differences in lactate concentration between conditions. In conclusion, PAP resulting from a heavy load prior back squat exercise improved total volume during resistance exercise. In addition, PAP was effective to increase force production during MVIC, but there was no relationship between relative 1RM values and the PAP response in trained men.

Moderate aerobic exercise-induced cytokines changes are disturbed in PPARα knockout mice.

The nuclear transcriptional factor peroxisome proliferator activated receptor alpha (PPARα) plays a role in regulating genes involved in lipid metabolism, adipogenesis and inflammation. We aimed to assess the role of PPARα on exercise-mediated locally produced cytokines in adipose fat deposits and skeletal muscle. C57BL/6 (WT) and PPARα knockout (PPARα-/-) mice were examined. Each genotype was randomly subdivided into three groups: non-exercised, and euthanized 2 or 24 h after a moderate aerobic exercise session (run on a treadmill at 60% of maximum speed for 1 h). Fat content in gastrocnemius muscle and lipolytic activity in isolated adipose tissue from mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue were evaluated. In addition, Interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) content were evaluated by ELISA. WT mice showed a maximum lipolysis rate, as well as higher IL-6, IL-10, and IL10/TNF-α ratio values 2 h post-exercise (RPAT only) compared with PPARα-/- mice. Taken together, our data suggests that PPARα knockout mice exhibited reduced lipolysis and anti-inflammatory response in adipose tissue following exercise, PPARα appears to play an important role in immunomodulatory and lipolysis signaling after acute moderate exercise.

High- and moderate-intensity training modify LPS-induced ex-vivo interleukin-10 production in obese men in response to an acute exercise bout.

The aim of this study was to evaluate the inflammatory (peripheral and lipopolysaccharide (LPS)-stimulated released from whole blood) and metabolic (glucose and insulin) profile of inactive obese men in response to two isoenergetic models of aerobic exercise training (~300  kcal each exercise session). Twenty-two participants (28.7 ± 1.6 years; BMI = 34.4 ± 0.1 kg/m2) were randomized into two groups: I) HIIT: high-intensity interval training (10× 1 bout: 1 min - 100% Maximal Aerobic Velocity) or II) MICT: moderate-intensity continuous training (65% Maximal Aerobic Velocity; kcal equal to HIIT). Both groups trained three times per week for 6-weeks. Fasting blood samples were collected before and 0, 30, and 60 min after exercise during the first and last training sessions for evaluation of: I) MIP-1ɑ, insulin, glucose, visceral and subcutaneous fat depots, oral glucose tolerance test, and homeostatic model assessment of insulin resistance (HOMA-IR) index; II) Peripheral (TNF-α, IL-6, and IL-10) and LPS-stimulated release of TNF-α and IL-10 were analyzed before, 0, and 60 min after sessions. IL-6 concentration remained elevated up to 60-min after the acute exercise session (p < 0.001), and IL-10 concentration was higher after 30 and 60-min (p = 0.001) compared to rest, independent of training period and protocol. AUC of IL-10 presented effect of type of training (p = 0.023) with MICT group showed significantly higher values than the HIIT. The ex-vivo assay showed higher IL-10 secretion in response to LPS immediately (p = 0.003) after both acute MICT and HIIT exercise sessions, independent of training period. Fifteen subjects presented decreased HOMA-IR after 6-weeks and seven presented an increase in this index. When we excluded the two least responsive subjects, it was possible to observe a decrease in HOMA-IR (p = 0.020) after training. Taken together, our results suggest that both HIIT and MICT (with same energy expenditure) promote similar effects on HOMA-IR and led to elevations in IL-10 production in LPS-stimulated whole blood, suggesting that leukocytes had an enhanced ability to secrete anti-inflammatory cytokines after the exercise bout.

Macrophage immunophenotype but not anti-inflammatory profile is modulated by peroxisome proliferator-activated receptor gamma (PPARγ) in exercised obese mice.

Moderate aerobic training may be therapeutic for chronic low-grade inflammatory diseases due to the associated anti-inflammatory response that is mediated by immune cells. The peroxisome proliferator-activated receptor gamma (PPARγ) regulates the M1 (pro-inflammatory) and M2 (anti-inflammatory) polarization, as well as the immunometabolic response of macrophages. Against this background, the present study seeks to clarify whether the conditional deletion of PPARγ in macrophages would have any effect on the anti-inflammatory role of moderate aerobic training. To test this hypothesis, two mice strains were used: PPARγ LyzCre+/+ (KO) and littermates control animals (WT). Each genotype was divided into 1) sedentary high-fat diet (HF) and 2) high-fat diet and moderate aerobic training (HFT) (n = 5-8 per group). The experimental protocol lasted for 12 weeks, comprising 4 weeks of HF diet only and 8 weeks of HF diet and aerobic training (5 times/week, 50-60 minutes/day at 60% of maximum speed). Metabolic analyses were carried out on the serum glucose homeostase, adipose tissue morphology and cytokine content, and macrophage cytokine production.Immunophenotyping and gene expression were also performed. KO male mice were more prone to hypertrophy in the subcutaneous adipose tissue, though only the IL-1ß (p = 0.0049) was higher compared to the values observed in WT animals. Peritoneal macrophages from KO animals exhibited a marked inflammatory environment with an increase in TNF-α (p = 0.0008), IL- 1ß (p = 0.0017), and IL-6 (p < 0.0001) after lipopolysaccharide stimulation. The moderate aerobic training protected both genotypes from weight gain and reduced the caloric intake in the KO animals. Despite the attenuation of the M2 marker CD206 (p < 0.001) in the absence of PPAR-γ, the aerobic training modulated cytokine production in LPS stimulated peritoneal macrophages from both genotypes, reducing proinflammatory cytokines such as TNF-α (p = 0.0002) and IL-6 (p < 0.0001). Overall, our findings demonstrate the essential role of PPARγ in macrophage immunophenotypes. However, the deletion of PPARγ did not inhibit the exercise-mediated anti-inflammatory effect, underscoring the important role of exercise in modulating inflammation.

Effects of turmeric extract supplementation on inflammation and muscle damage after a half-marathon race: a randomized, double-blind, placebo-controlled trial.

PURPOSE: Strenuous exercise induces inflammation and muscle damage. Turmeric (Curcuma longa L.) is a widely used spice that exhibits potent anti-inflammatory response and appears to decrease indirect markers of muscle damage. A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effects of Curcuma longa L. extract (CLE) on inflammation and muscle damage after a half-marathon race. METHODS: Twenty-eight healthy, normal-weight men were randomly assigned to one of two groups: (1) CLE (3 capsules per day, 500 mg each); or (2) placebo (PLA, 3 capsules per day, 500 mg of microcrystalline cellulose). Participants received the intervention for 4 weeks and immediately before and after the half-marathon race. Creatine kinase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, myoglobin, interleukins 6 and 10 were assessed at baseline, immediately before, after, and at 2, 24, and 48 h after the half-marathon race. RESULTS: The half-marathon race increased markers of inflammation and muscle damage. A greater increase in interleukin-10 was observed in the CLE group immediately after the competition compared to the PLA group (7.54 ± 1.45 vs 5.25 ± 0.59 pg/mL; p < 0.05; d = 0.55). Myoglobin concentration was lower 2 h after the race in participants from the CLE group compared to the PLA group (62.10 ± 8.26 vs 107.85 ± 18.45 ng/mL; p = 0.01; d = 0.86). CONCLUSION: Curcuma longa L. extract supplementation leads to an increase in IL-10 and decreased myoglobin in recreational male runners after a half-marathon race. TRIAL REGISTRATION NUMBER: U1111-1179-6335, February 13, 2016.

Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors γ deletion in macrophages.

BACKGROUND: Exercise is a powerful tool for prevention and treatment of many conditions related to the cardiovascular system and also chronic low-grade inflammation. Peroxisome proliferator-activated receptors γ (PPARγ) exerts an import role on the regulation of metabolic profile and subsequent inflammatory response, especially in macrophages. PURPOSE: To investigate the effects of 8-week moderate-exercise training on metabolic and inflammatory parameters in mice with PPARγ deficiency in myeloid cells. METHODS: Twelve-week old mice bearing PPARγ deletion exclusively in myeloid cells (PPARγlox/lox Lys Cre -/+ , knockout [KO]) and littermate controls (PPARγlox/lox Lys Cre -/- , wild type [WT]) were submitted to 8-week exercise training (treadmill running at moderate intensity, 5 days/week). Animals were evaluated for food intake, glucose homeostasis, serum metabolites, adipose tissue and peritoneal macrophage inflammation, and basal and stimulated cytokine secretion. RESULTS: Exercise protocol did not improve glucose metabolism or adiponectin concentrations in serum of KO mice. Moreover, the absence of PPARγ in macrophages exacerbated the proinflammatory profile in sedentary mice. Peritoneal cultured cells had higher tumor necrosis factor-α (TNF-α) secretion in nonstimulated and lipopolysaccharide (LPS)-stimulated conditions and higher Toll-4 receptor (TLR4) gene expression under LPS stimulus. Trained mice showed reduced TNF-α content in adipose tissue independently of the genotype. M2 polarization ability was impaired in KO peritoneal macrophages after exercise training, while adipose tissue-associated macrophages did not present any effect by PPARγ ablation. CONCLUSION: Overall, PPARγ seems necessary to maintain macrophages appropriate response to inflammatory stimulus and macrophage polarization, affecting also whole body lipid metabolism and adiponectin profile. Exercise training showed as an efficient mechanism to restore the immune response impaired by PPARγ deletion in macrophages.

Interleukin-10 responses from acute exercise in healthy subjects: A systematic review.

PURPOSE: Interleukin 10 (IL-10) is a cytokine that plays a critical role with potent anti-inflammatory properties when produced during exercise, limiting host immune response to pathogens and preventing tissue damage. The purpose of this systematic review was to assess the response of IL-10 after acute exercise session in healthy adults. METHODS: Databases of Ovid Medline (1978-2016), CINAHL (1998-2016), EMBASE (2003-2016), SportDiscus (1990-2016), and Web of Science library (1990-2016) were carefully screened. Clinical trials comparing exercise types in healthy individuals were included for pooled analysis. The trials of exercise were methodologically appraised by PEDro Scale. RESULTS: Twelve randomized controlled and crossover trials containing 176 individuals were identified for inclusion. The Kruskal-Wallis test showed no significant differences between type of exercise and the corresponding values in IL-10 [X2(4) = 2.878; p = 0.449]. The duration of exercise was significantly correlated with increase in IL-10 changes (Pearson's r = 1.00, 95%CI: 0.015-0.042, p < 0.0001) indicating that 48% of the variation in IL-10 levels can be explained by the duration of the exercise performed. In addition, despite a linear increase, we did not find a significant correlation with the intensity of exercise and IL-10 changes (Pearson's r = 0.218, 95%CI: -0.554-0.042, p < 0.035). CONCLUSION: Overall, the duration of the exercise is the single most important factor determining the magnitude of the exercise-induced increase of plasma IL-10.

Anti-inflammatory response to acute exercise is related with intensity and physical fitness.

PURPOSE: The relationship between inflammatory markers and energetic metabolism has been explored. However, the relationship between exercise intensity and fitness status is unclear, and it is necessary to understand this relationship to apply specific exercise guidance. The purpose of the study was to analyze metabolic and inflammatory responses imposed by acute exercise sessions performed at moderate, heavy, and severe intensities and their relationship with the physical fitness status. METHODS: Nineteen healthy male volunteers performed three acute exercise sessions until exhaustion or up to 60 minutes on a cycle ergometer at moderate (90% of first ventilatory threshold [VT1]), heavy (midpoint between VT1 and second ventilatory threshold [VT2]), and severe (midpoint between VT2 and maximal aerobic power) intensities. Blood lactate, glucose, NEFA, endotoxin, and cytokines were determined for each exercise session. Peripheral and lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 was analyzed before, after, and 60 minutes after sessions. RESULTS: In peripheral blood, severe intensity increased lactate, endotoxin, and TNF-α immediately after exercise and glucose at 60 min after exercise. There was a trend for IL-10 increase at 60 minutes after exercise in peripheral blood. Immediately after exercise, LPS-stimulated TNF-α, IL-6, IL-6/IL-10 ratio, and lactate levels were higher in the severe intensity while nonester fatty acid levels decreased at this time. At 60 minute after exercise, higher concentrations of glucose and a trend for increased IL-10 were observed in severe intensity. A positive correlation was observed between maximal aerobic power and IL-10 ( r = 0.513; P = 0.042), and negative correlations between maximal aerobic power and endotoxin ( r = -0.531; P = 0.034) and lactate ( r = -0.538; P = 0.031) in heavy intensity. CONCLUSION: Our data show a novel finding that higher cytokine responses occur at higher intensities, mainly in severe intensity. However, the anti-inflammatory (IL-10) response was physical fitness-dependent.

Exercise-induced AMPK activation and IL-6 muscle production are disturbed in adiponectin knockout mice.

BACKGROUND: Adiponectin exhibits anti-inflammatory actions and is mainly expressed in adipose tissue. However, recent studies have shown that adiponectin can also be secreted by skeletal muscle fibers with autocrine and paracrine effects. OBJECTIVES: To analyze the role of adiponectin in the metabolic and inflammatory response of skeletal muscle after acute exhaustive aerobic exercise. METHODS: C57BL/6 (WT) and adiponectin knockout (AdKO) mice underwent four days of treadmill running adaptation and at the fifth day, they performed an incremental maximum test to determine the maximum speed (Vmax). Acute exercise consisted of one hour at 60% Vmax. Mice were euthanatized 2 and 24 h after acute exercise session. RESULTS: Serum and gastrocnemius adiponectin increased after 2-hours of acute exercise. NEFA concentrations were lower in non-exercise AdKO, and decreased 2-hours after exercise only in WT. No differences were found in muscle triacylglycerol content; however, glycogen content was higher in AdKO in non-exercise (p-value = 0.005). WT showed an increase in AMP-activated protein kinase (AMPK) phosphorylation 2-hours after exercise and its level went back to normal after 24-hours. Otherwise, exercise was not able to modify AMPK in the same way as in AdKO. WT showed an increase in the phosphorylation of ACC (Ser79) 2-hours after exercise and return to normal after 24-hours of exercise (p-value < 0.05), kinects that was not observed in AdKO mice. IL-10 and IL-6 concentration was completely different among genotypes. In WT, these cytokines were increased at 2 (p-value < 0.01) and 24 h (p-value < 0.001) after exercise when compared with AdKO. NF-κBp65 protein and gene expression were not different between genotypes. CONCLUSION: Adiponectin influences muscle metabolism, mainly by the decrease in exercise-induced AMPK phosphorylation, inflammatory profile and IL-6 in the muscle.

Intradialytic Resistance Training Improves Functional Capacity and Lean Mass Gain in Individuals on Hemodialysis: A Randomized Pilot Trial.

OBJECTIVE: To compare the effects of high vs moderate loads of intradialytic resistance training (RT) on body composition, sarcopenia prevalence, functional capacity, inflammatory markers, and quality of life (QoL) in individuals on hemodialysis. DESIGN: A pilot randomized clinical trial. SETTING: Two hemodialysis centers. PARTICIPANTS: Individuals on hemodialysis (N=80; 51% men, aged 30-75y) in treatment for at least 3 months, adequately dialyzed (Kt/V≥1.2, where K is dialyzer clearance in mL/min, t is time, and V is volume of water) with vascular access via arteriovenous fistula. INTERVENTIONS: The 12 weeks of intradialytic RT was performed 3 times per week. The training groups were: high-load intradialytic group (HLG, 8-10 repetitions), moderate-load intradialytic group (MLG, 16-18 repetitions), and control group (CG, stretching exercise). The total training volume was equalized among training groups. MAIN OUTCOME MEASURES: Lean leg mass was assessed by a dual-energy x-ray absorptiometry; functional capacity was assessed by Short Physical Performance Battery and Timed Up and Go test; and QoL was assessed by Kidney Disease QoL Instrument, inflammatory markers, and sarcopenia. RESULTS: After the training period, the HLG increased lean leg mass compared with the CG. The HLG also displayed improvements in the pain and physical function domains. The skeletal muscle index and functional capacity increased in both RT protocols. The prevalence of sarcopenia was reduced 14.3% and 25% in the MLG and HLG, respectively, while there was an increase of 10% in the CG. No differences were observed in cytokines after intervention. CONCLUSIONS: High-load intradialytic RT was associated with gains in lean leg mass and QoL while functional capacity, appendicular muscle mass, and sarcopenia status were improved regardless of the RT load.

Capsaicin supplementation increases time to exhaustion in high-intensity intermittent exercise without modifying metabolic responses in physically active men.

PURPOSE: The purpose of this study was to investigate the acute effect of capsaicin supplementation on performance and physiological responses during high-intensity intermittent exercise (HIIE). METHOD: Thirteen physically active men (age = 24.4 ± 4.0 years; height = 176.4 ± 6.9 cm; body mass = 78.7 ± 13.8 kg; running training per week = 3.9 ± 0.9 h) performed an incremental running test to determine peak oxygen uptake ([Formula: see text]) and the speed associated with [Formula: see text] (s[Formula: see text]). Thereafter, subjects completed two randomized, double-blind HIIE (15s:15 s at 120% s[Formula: see text]) trials 45-min after consuming capsaicin (12 mg) or an isocaloric placebo. Time to exhaustion, blood lactate concentration, oxygen consumption during and 20 min post-exercise, energy expenditure, time spent above 90% of [Formula: see text], and the rate of perceived exertion were evaluated. RESULTS: There was no difference between capsaicin and placebo for any variable except time to exhaustion [capsaicin: 1530 ± 515 s (102 efforts) vs placebo: 1342 ± 446 s (89 efforts); p < 0.001]. CONCLUSION: In conclusion, capsaicin supplementation increased time to exhaustion in high-intensity intermittent exercise without modifying the metabolic response of exercise or the rate of perceived exertion in physically active men. Capsaicin could be used to increase the training load during specific exercise training sessions.

Timing of high-intensity intermittent exercise affects ad libitum energy intake in overweight inactive men.

The present study sought to clarify the impact of exercise intensity and timing on energy intake and appetite-related blood variables. Fourteen inactive overweight men were included in the study. Firstly, maximal aerobic power (MAP) was measured. Then, participants randomly performed 5 experimental sessions consisting of 30 min of steady-state exercise (SSE) at 50% of MAP, high-intensity intermittent exercise (HIIE) with 30s repetitions at MAP and 30s of passive recovery or no exercise (CTRL). Sessions were performed 1h (SSE1h and HIIE1h) or 2.5h (SSE2.5h and HIIE2.5h) after the consumption of a standardized breakfast. An ad libitum buffet was offered 3.5h after the completion of the breakfast. Absolute energy intake (EI) and relative energy intake (REI) (relative energy intake = energy intake - energy expenditure from exercise) were measured. Appetite (hunger, fullness and desire for specific foods) scores and circulating concentration of insulin and IL-6 were determined at 1h, 1.75h, 2.5h and 3.25h after breakfast while lactate was measured post-exercise. EI was greater after the CTRL session compared to HIIE2.5h (5045.9 ±â€¯1873.5 kJ vs. 3716.1 ±â€¯1688.7 kJ). REI was greater for the CTRL session (5045.9 ±â€¯1873.5 kJ) than HIIE1h (3386.5 ±â€¯1660.1 kJ), HIIE2.5h (2508.5 ±â€¯1709.3 kJ) and SSE2.5h (3426.6 ±â€¯1788.0 kJ). Higher hunger scores were observed following the CRTL session with respect to those of HIIE2.5h. Insulin and IL-6 concentrations were greater after HIIE1h and SSE1h with respect to those obtained after HIIE2.5h, SSE2.5h and CTRL. Lactate concentrations were higher in HIIE1h and HIIE2.5h compared to those of SSE1h and SSE2.5h. These results show that HIIE performed 2.5h after a breakfast reduced appetite (hunger scores) and EI through mechanism that need to be characterized. This approach can be applied to individuals aiming to create an energetic deficit.