Direct assessment of leukocyte signalling and cytokine secretion reveals exercise intensity-dependent reductions in anti-inflammatory cytokine action.

Circulating interleukin (IL)-6 and IL-10 concentrations are widely used to evaluate the anti-inflammatory effects of exercise but do not capture cytokine action at the cellular level. Whether and how acute exercise impacts anti-inflammatory cytokine action in humans is unknown. To determine how exercise intensity and pattern impact IL-6 and IL-10 action in blood leukocytes, 16 active adults (eight males/eight females; age: 30 ± 3 years; body mass index: 22.8 ± 2.3 kg/m2; V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ : 51 ± 6 mL/kg/min) completed a no-exercise control condition (CTL) or isocaloric bouts of cycling performed below (moderate continuous exercise; MCE) or above (heavy continuous or heavy intermittent exercise; HCE or HIE, respectively) lactate threshold. Venous blood (before, after, 30 min after and 90 min after exercise) was analysed for immune cell subpopulations, plasma cytokine concentrations, anti-inflammatory cytokine action and monocyte phenotype. Exercise induced rapid leukocytosis (P < 0.001) and increased plasma IL-6 (P < 0.001), IL-10 (P = 0.0145) and tumour necrosis factor-⍺ (TNF-⍺) (P = 0.0338) concentrations in an intensity-dependent manner (HCE and/or HIE vs. CTL). These systemic changes coincided with a diminished ability of IL-10/6 to phosphorylate STAT3 (P < 0.001) and inhibit TNF-⍺ secretion (P = 0.0238) in blood leukocytes following HCE and HIE. Monocyte polarization experiments revealed lower CD80 [MCE (P = 0.0933) and HIE (P = 0.0187) vs. CTL] and a tendency for higher CD163 expression (HCE vs. CTL, P = 0.0985), suggesting that hyporesponsiveness to anti-inflammatory cytokine action does not impede the ability of exercise to promote an anti-inflammatory monocyte phenotype. These findings provide novel insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise. KEY POINTS: Circulating cytokine concentrations are frequently used to evaluate the anti-inflammatory effects of exercise but may not capture changes in cytokine action occurring at the cellular level. We directly assessed anti-inflammatory cytokine action - measured using a combination of intracellular signalling and cytokine secretion ex vivo - in distinct immune cell subpopulations after acute calorie-matched exercise bouts differing in intensity and pattern. Anti-inflammatory cytokine action was blunted following higher intensity exercise despite corresponding increases in circulating cytokine concentrations and immune cell counts. Changes in cytokine action were not explained by changes in cytokine receptor expression on circulating immune cells. Our findings provide new insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise.

Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue.

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity.

Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported. Methods: In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment. Results: SRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1ß serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.

Ten weeks of Capsicum annuum L. extract supplementation did not change adipose tissue-derived hormones, appetite, body composition, and muscle strength when combined with resistance training in healthy untrained men: A clinical trial study.

Capsiate (CAP) is a nonpungent capsaicin analog (Capsicum annuum L. extract) that has been studied as a potential antiobesity agent. However, the interaction between chronic CAP supplementation and resistance training is not clear. The purpose of this study was to examine the changes in adipose tissue-derived hormones, body composition, appetite, and muscle strength after 10 weeks of resistance training, combined with chronic CAP supplementation in healthy untrained men. We hypothesized that CAP could induce higher benefits when combined with resistance training after 10 weeks of intervention compared to resistance training alone. Twenty-four young men (age, 22.0 ± 2.9) were randomized to either capsiate supplementation (CAP = 12 mg/day) or placebo (PL), and both groups were assigned to resistance training. Body composition, leptin and adiponectin concentrations, subjective ratings of appetite, energy intake, and exercise performance were assessed at before and after 10 weeks of progressive resistance training. There was a significant increase in body mass (P < .001), fat-free mass (CAP: 58.0 ± 7.1 vs. post, 59.7 ± 7.1 kg; PL: pre, 58.4 ± 7.3 vs. post, 59.8 ± 7.1 kg; P < .001), resting metabolic rate (CAP: pre, 1782.9 ± 160.6 vs. post, 1796.3 ± 162.0 kcal; PL: pre, 1733.0 ± 148.9 vs. post, 1750.5 ± 149.8 kcal; P < .001), maximal strength at 45 leg press (P < .001) and bench press (P < .001) in both groups, but no significant (P > .05) supplementation by training period interaction nor fat mass was observed. For subjective ratings of appetite, energy intake, leptin, and adiponectin, no significant effect of supplementation by training period interaction was observed (P > .05). In conclusion, 10 weeks of resistance training increased total body weight, muscle mass, and maximum strength in healthy untrained men; however, CAP supplementation (12 mg, 7 days per week) failed to change adipose tissue-derived hormones, appetite, body composition and muscle strength in this population. Registered under Brazilian Registry of Clinical Trials (RBR-8cz9kfq).

Environmental Enrichment in Cancer as a Possible Tool to Combat Tumor Development: A Systematic Review.

This systematic review aims to evaluate the influence of environmental enrichment (EE) on oncological factors in experimental studies involving various types of cancer models. A comprehensive search was conducted in three databases: PubMed (161 articles), Embase (335 articles), and Scopus (274 articles). Eligibility criteria were applied based on the PICOS strategy to minimize bias. Two independent researchers performed the searches, with a third participant resolving any discrepancies. The selected articles were analyzed, and data regarding sample characteristics and EE protocols were extracted. The outcomes focused solely on cancer and tumor-related parameters, including cancer type, description of the cancer model, angiogenesis, tumor occurrence, volume, weight, mice with tumors, and tumor inhibition rate. A total of 770 articles were identified across the three databases, with 12 studies meeting the inclusion criteria for this systematic review. The findings demonstrated that different EE protocols were effective in significantly reducing various aspects of tumor growth and development, such as angiogenesis, volume, weight, and the number of mice with tumors. Furthermore, EE enhanced the rate of tumor inhibition in mouse cancer models. This systematic review qualitatively demonstrates the impacts of EE protocols on multiple parameters associated with tumor growth and development, including angiogenesis, occurrence, volume, weight, and tumor incidence. Moreover, EE demonstrated the potential to increase the rate of tumor inhibition. These findings underscore the importance of EE as a valuable tool in the management of cancer.

Impact of Breaking up of Sitting Time on Anti-inflammatory Response Induced by Extracellular Vesicles.

Physical inactivity and sedentary behaviors (SB) have promoted a dramatic increase in the incidence of a host of chronic disorders over the last century. The breaking up of sitting time (i.e., sitting to standing up transition) has been proposed as a promising solution in several epidemiological and clinical studies. In parallel to the large interest it initially created, there is a growing body of evidence indicating that breaking up prolonged sedentary time (i.e., > 7 h in sitting time) could reduce overall mortality risks by normalizing the inflammatory profile and cardiometabolic functions. Recent advances suggest that the latter health benefits, may be mediated through the immunomodulatory properties of extracellular vesicles. Primarily composed of miRNA, lipids, mRNA and proteins, these vesicles would influence metabolism and immune system functions by promoting M1 to M2 macrophage polarization (i.e., from a pro-inflammatory to anti-inflammatory phenotype) and improving endothelial function. The outcomes of interrupting prolonged sitting time may be attributed to molecular mechanisms induced by circulating angiogenic cells. Functionally, circulating angiogenic cells contribute to repair and remodel the vasculature. This effect is proposed to be mediated through the secretion of paracrine factors. The present review article intends to clarify the beneficial contributions of breaking up sitting time on extracellular vesicles formation and macrophage polarization (M1 and M2 phenotypes). Hence, it will highlight key mechanistic information regarding how breaking up sitting time protocols improves endothelial health by promoting antioxidant and anti-inflammatory responses in human organs and tissues.

The growing field of immunometabolism and exercise: Key findings in the last 5 years.

This perspective review highlights the impact of physical exercise on immunometabolic responses in the past 5 years. Understanding immunometabolism as a part of immunological research is essential. Furthermore, the roles of both acute and chronic effects of physical exercise on health, aging, and chronic diseases in immunometabolic changes should be elaborated. In immune cells, ß2 adrenergic signaling stimulates the preferential mobilization of inflammatory phenotypes, such as CD16+ monocytes and CD8+ T cells, into the bloodstream after a physical exercise session. The mobilization of immune cells is closely related to the availability of energetic substrates for the cell and mechanisms associated with the uptake and oxidation of fatty acids and glucose. These cells, especially senescent T cells, are mobilized to the peripheral tissues and undergo apoptotic signaling, stimulating the creation of a "vacant space" where new cells will be matured and replaced in the circulation. This results in the upregulation of the expression and secretion of anti-inflammatory cytokines (IL-10 and IL-1ra), leading to increased regulatory immune cells that provide immunoregulatory properties. Thus, we suggest that a significant nutrient available to the cell will favor oxidative metabolism, augment ATP production, and consequently maintain the immune cells in their quiescent state, as well as promote rapid activation function. Therefore, based on the studies discussed in this perspective review, we highlight the importance of performing moderate-intensity continuous and high-intensity intermittent aerobic exercises, due to a higher magnitude of energetic demand and release of anti-inflammatory cytokines (IL-6 and IL-10).

Occupational Physical Activity Was Associated With Disability Levels at 6-Month Follow-Up of Patients With Chronic Nonspecific Low Back Pain: A Prospective Cohort Study.

BACKGROUND: Physical activity plays an important role in the prognosis of chronic low back pain (LBP); however, whether physical activity predicts pain intensity and disability remains unknown. This study investigated whether objective and subjective physical activity measures predict pain intensity and disability levels 6 months later in patients with chronic LBP. METHODS: Patients with chronic LBP seeking care at 2 outpatient physiotherapy clinics were recruited. At baseline assessment, we collected anthropometric/sociodemographic data, duration of symptoms, pain intensity, disability, and physical activity (accelerometer and questionnaire). After 6 months, we reassessed pain and disability. Multivariable regression analyses were performed to investigate the association of physical activity measures with pain and disability at follow-up. RESULTS: A total of 179 patients with chronic LBP were included. High occupational physical activity at baseline predicted disability at 6-month follow-up (B = 1.22; 95% confidence interval, 0.21 to 2.21) after controlling for age and baseline disability, meaning that for every 1-point increase in occupational physical activity, disability increased on average by 1.22 point. The remaining physical activity measures showed no association with pain intensity or disability at follow-up. CONCLUSION: Higher perceived levels of occupational physical activity predicted higher disability levels at 6-month follow-up in patients with chronic LBP.

Sex differences in IL-10's anti-inflammatory function: greater STAT3 activation and stronger inhibition of TNF-α production in male blood leukocytes ex vivo.

Interleukin-10 (IL-10) inhibits proinflammatory cytokine production in blood leukocytes-an effect mediated by signal transducer and activator of transcription 3 (STAT3) activation. To examine potential sex-based differences in IL-10's anti-inflammatory function, we treated whole blood from healthy males and females (n = 16 participants of each sex; age: 28 ± 6 yr; body mass index: 23.5 ± 2.3 kg/m2) with increasing concentrations of IL-10 (1-100 ng/mL) and quantified changes in phosphorylated STAT3 (pSTAT3) in CD14+ monocytes and CD4+ lymphocytes via flow cytometry. In parallel, liposaccharide (LPS)-stimulated whole blood cultures were used to assess sex-based differences in IL-10's ability to inhibit tumor necrosis factor (TNF)-α production. IL-10 concentration dependently increased pSTAT3 median fluorescent intensity (MFI) in CD14+ and CD4+ cells (main effects of concentration, P < 0.01) with males exhibiting larger changes in pSTAT3 MFI in both cell types (main effects of sex, P < 0.01). Accordingly, IL-10-mediated inhibition of TNF-α production was more pronounced in males (main effect of sex, P < 0.01) with changes in other monocyte-derived cytokines (IL-1ß, IL-1RA, and IL-15) also supporting a sexual dimorphism in IL-10 action (P < 0.05). These sex-based differences were not explained by differences in circulating plasma IL-10 concentrations, basal IL-10 receptor expression in unstimulated CD14+ and CD4+ cells, nor the basal expression of IL-10 signaling proteins (STAT3, SHIP1, and p38 MAPK) in unstimulated peripheral blood mononuclear cells. We conclude that IL-10's anti-inflammatory function differs between male and female blood leukocytes ex vivo. This sexual dimorphism should be considered in future work investigating IL-10's anti-inflammatory action in humans as it may represent a mechanism contributing to sex differences in overall immune function.

Viral load is associated with mitochondrial dysfunction and altered monocyte phenotype in acute severe SARS-CoV-2 infection.

Monocytes play a major role in the initial innate immune response to SARS-CoV-2. Although viral load may correlate with several clinical outcomes in COVID-19, much less is known regarding their impact on innate immune phenotype. We evaluated the monocyte phenotype and mitochondrial function in severe COVID-19 patients (n = 22) with different viral burden (determined by the median of viral load of the patients) at hospital admission. Severe COVID-19 patients presented lower frequency of CD14 + CD16- classical monocytes and CD39 expression on CD14 + monocytes, and higher frequency of CD14 + CD16 + intermediate and CD14-CD16 + nonclassical monocytes as compared to healthy controls independently of viral load. COVID-19 patients with high viral load exhibited increased GM-CSF, PGE-2 and lower IFN-α as compared to severe COVID-19 patients with low viral load (p < 0.05). CD14 + monocytes of COVID-19 patients with high viral load presented higher expression of PD-1 but lower HLA-DR on the cell surface than severe COVID-19 patients with low viral load. All COVID-19 patients presented decreased monocyte mitochondria membrane polarization, but high SARS-CoV-2 viral load was associated with increased mitochondrial reactive oxygen species. In this sense, higher viral load induces mitochondrial reactive oxygen species generation associated with exhaustion profile in CD14 + monocytes of severe COVID-19 patients. Altogether, these data shed light on new pathological mechanisms involving SARS-CoV-2 viral load on monocyte activation and mitochondrial function, which were associated with COVID-19 severity.

Costly immunometabolic remodelling in disused muscle buildup through physical exercise.

The mechanisms underlying the immunometabolic disturbances during skeletal muscle atrophy caused by a plethora of circumstances ranging from hospitalization to spaceflight missions remain unknown. Here, we outline the possible pathways that might be dysregulated in such conditions and assess the potential of physical exercise to mitigate and promote the recovery of muscle morphology, metabolism and function after intervals of disuse. Studies applying exercise to attenuate disuse-induced muscle atrophy have shown a pivotal role of circulating myokines in the activation of anabolic signalling pathways. These muscle-derived factors induce accretion of contractile proteins in the myofibers, and at the same time decrease protein breakdown and loss. Regular exercise plays a crucial role in re-establishing adequate immunometabolism and increasing the migration and presence in the muscle of macrophages with an anti-inflammatory phenotype (M2) and T regulatory cells (Tregs) after disease-induced muscle loss. Additionally, the switch in metabolic pathways (glycolysis to oxidative phosphorylation [OXPHOS]) is important for achieving rapid metabolic homeostasis during muscle regeneration. In this review, we discuss the molecular aspects of the immunometabolic response elicited by exercise during skeletal muscle regeneration. There is not, nevertheless, consensus on a single optimal intensity of exercise required to improve muscle strength, mass and functional capacity owing to the wide range of exercise protocols studied so far. Despite the absence of agreement on the specific strategy, physical exercise appears as a powerful complementary strategy to attenuate the harmful effects of muscle disuse in different scenarios.

Exercise Training Protocols to Improve Obesity, Glucose Homeostasis, and Subclinical Inflammation.

The global pandemics of obesity and sedentarism are associated with poor quality of life and increased risks for development of inflammatory chronic diseases, including type 2 diabetes, cardiovascular diseases, and cancer. Physical activity is considered as an antidote to counteract the development of chronic sterile inflammatory diseases. Thus, we review the most promising exercise training protocols for promoting weight loss, improving glucose homeostasis, and reducing inflammation. We discuss the advantages and disadvantages of moderate-intensity continuous aerobic training, high-intensity aerobic training, and combined (aerobic + resistance) training. Our aim with this chapter is to provide evidence and guidance for choosing the most appropriate protocols of exercise training according to the goals of the patient.

Acute Response to Capsiate Supplementation at Rest and during Exercise on Energy Intake, Appetite, Metabolism, and Autonomic Function: A Randomized Trial.

OBJECTIVE: The purpose of the present study was to examine the effect of capsiate supplementation on energy intake, self-reported appetite-related sensations, energy expenditure, fat oxidation, and autonomic parameters with and without an exercise intervention. METHODS: Thirteen healthy men completed four randomized trials: two trials for the control condition (without exercise), one with capsiate supplementation (CTRLcap) and one with a placebo (CTRLpla), and two trials for the exercise condition, one with capsiate supplementation (EXcap) and one with placebo (EXpla). Exercise sessions were performed 150 min after the consumption of a standardized breakfast, and supplementation 115 min after consumption of breakfast. An ad libitum buffet was offered 200 min following the completion of the standardized breakfast, and energy intake (EI) and relative energy intake (REI) (relative energy intake = energy intake - energy expenditure related to exercise) were evaluated. RESULTS: There were no significant effects on EI, self-reported appetite sensations, fat oxidation, and energy expenditure. REI was reduced in conditions involving EX when compared to CTRL. A low-frequency to high-frequency ratio for heart rate variability was higher in CTRLcap (1.6 ± 1.1) vs. CTRLpla (1.2 ± 0.9) (p = 0.025; d = 0.39). CONCLUSION: Acute capsiate supplementation combined with aerobic exercise has limited effects on the examined variables (EI, REI, fat oxidation, energy expenditure, and autonomic parameters), while changes in the autonomic nervous system function in the absence of exercise may have occurred without influencing other variables. CLINICAL TRIAL REGISTRATION: ensaiosclinicos.gov.br number, RBR-5pckyr https://ensaiosclinicos.gov.br/rg/RBR-5pckyr.

The impact of intradialytic exercise on immune cells expressing CCR5+ in patients with chronic kidney disease: A cross-over trial.

The C-C chemokine receptor type 5 (CCR5) plays a role in the immunopathogenesis of chronic kidney disease (CKD). Exercise has anti-inflammatory properties that may contribute to the rehabilitation of CKD patients. To date, the impact of the intradialytic exercise on CCR5 expression in monocytes and lymphocytes of CKD patients is unknown. We aimed to evaluate the effects of an acute intradialytic moderate-intensity exercise on CD4+CCR5+ T-cells and CD14+CCR5+ monocytes of elderly individuals with Chronic Kidney Disease (CKD). Eight CKD elderly patients performed a single bout of 20 min intradialytic exercise and a control hemodialysis (HD) session. Blood samples were collected at baseline, during and immediately after the trials. HD therapy increased the peripheral frequency of CD4+CCR5+ T-cells. The systemic CCL5 levels and the peripheral CD14+CCR5+ proportions increased during and after HD therapy. No significant alterations in CD4+CCR5+ and CD14+CCR5+ proportions or CCL5 levels were identified in CKD patients during and after intradialytic exercise. A negative correlation between the peripheral frequency of CD14+CCR5+ and the creatinine levels was identified in the intradialytic exercise session. A single moderate-intensity intradialytic exercise imposes an immunomodulatory impact in CKD elderly patients, preventing an excessive inflammatory response induced by hemodialysis.

Testosterone and lean mass show a positive correlation with the technical performance of footballers.

BACKGROUND: Monitoring technical performance during a soccer match has become an indispensable practice, since the players perform different functions within the tactical system adopted by the team, resulting in specific technical actions that are fully responsive to the individual technical level of each player. Thus, current study aimed to investigate the possible direct and mediating relationship between salivary testosterone and the technical performance of semi-professional footballers during a training game. METHODS: To characterize the sample, the anthropometric profile, body composition, biological maturation, lower limb power, speed, estimation of maximum oxygen consumption, and physical performance were used. To determine testosterone concentrations, saliva was collected before and after the training game, for subsequent measurement using enzyme immunoassay (ELISA) and Salimetrics Kits. For quantification of technical performance and participation with the ball during the training game, scout software was used from the footage of the training game. The reliability of the technical performance analyses was determined through the repetition test of two attempts (Cohen's Kappa agreement index). RESULTS: The direct relationship between postgame testosterone and total participation with the ball in the second half; the direct relationship between the percentage of lean mass with postgame testosterone and an apparent relationship between percentage of lean mass and total participation with the ball from the set of relations mediated by postgame testosterone concentrations. CONCLUSIONS: The results suggest that testosterone concentrations combined with high levels of lean mass may have an important role in the technical performance and participation with the ball of semi-professional footballers.

Type and Intensity as Key Variable of Exercise in Metainflammation Diseases: A Review.

Monocyte and lymphocyte subpopulations exhibit functions that vary between the anti- and pro-inflammatory spectrum, such as classic CD16- and non-classical CD16+monocytes, as well as T helper 2 lymphocytes (Th2), the Th1/Th17 lymphocytes ratio, and T regulatory lymphocytes (Treg). Metabolic disease-associated inflammation is accompanied by an imbalance in monocyte and lymphocyte phenotypes and functionality, as well as a stronger proportion of inflammatory subpopulations. These changes appear to be important for the development and progression of diseases like diabetes and cardiovascular disease. On the other hand, the regular practice of physical exercise is an important tool to restore the functionality of monocytes and lymphocytes, and to balance the subtypes ratio. However, key variables regarding exercise prescription, such as the type of exercise, intensity, and volume differentially impact on the acute and chronic immune response in individuals diagnosed with meta-inflammation diseases. Here, we discuss the impact of different physical exercise protocols, acutely and chronically, on monocytes and lymphocytes of individuals with metabolic disease-associated inflammation. In this review, we focus on the best effects of different exercise protocols to dose the "exercise pill" in different inflammatory status.

Role of Neuronal Guidance Cues in the Pathophysiology of Obesity: A Peripheral and Central Overview.

Obesity is associated with an exacerbated synthesis and secretion of several molecules, which culminates in chronic low-grade inflammation and insulin resistance. Such conditions affect molecular and physiological responses of several organs and, if not resolved, predispose the obese patients to other diseases such as Type 2 diabetes, atherosclerosis, cancer, neural injuries, and cognitive impairments. A microenvironment with an excess of pro-inflammatory cytokines released by different cells, including immune and adipose cells lead to metabolic and non-metabolic diseases during obesity. In this context, the role of neuronal guidance cues named netrin, semaphorin and ephrin is novel. Specifically, the available literature indicates that besides their classic role as molecules that guide the axon to its target site, the neuronal guidance cues exhibit immunomodulatory functions from adipose tissue to the neural environment. In the current narrative review, we discuss the participation of the neuronal guidance cues on the physiology and pathophysiology of obesity. We also discuss the feedback loop of obesity on the netrin, semaphorin and ephrin functions that impair the structure and function of the brain. The integrative view of the neuronal guidance cues can be relevant in designing new treatments focus on attenuating metabolic and immune disorders in obese patients and reduce the risk of acquiring diseases such as Type 2 diabetes, atherosclerosis, cancer, and neural injuries.

Appetite Is Suppressed After Full-Body Resistance Exercise Compared With Split-Body Resistance Exercise: The Potential Influence of Lactate and Autonomic Modulation.

ABSTRACT: Conrado de Freitas, M, Ricci-Vitor, AL, de Oliveira, JVNS, Quizzini, GH, Vanderlei, LCM, Silva, BSA, Zanchi, NE, Cholewa, JM, Lira, FS, and Rossi, FE. Appetite is suppressed after full-body resistance exercise compared with split-body resistance exercise: the potential influence of lactate and autonomic modulation. J Strength Cond Res 35(9): 2532-2540, 2021-The purposes of this study were to investigate the effects of full- vs. split-body resistance training on appetite and leptin response and to verify the potential involvement of lactate and autonomic modulation during this response in trained men. Twelve recreationally resistance-trained men (age = 26.1 ± 5.5 years) performed 3 randomized trials in 3 conditions: upper body (UB), lower body (LB), and full body (FB). The subjective rating of hunger was obtained through a visual analog scale. Leptin and lactate concentration were evaluated at rest, immediately after exercise, and during recovery. Heart rate variability in the time and frequency domains was recorded at baseline and during recovery (until 60 minutes after exercise) to assess autonomic modulation. The FB condition induced lower subjective hunger ratings than the UB at Post-1 hour (p < 0.05) and a significant difference in the area under the curve between conditions (p = 0.028) with lower hunger sensation for FB in relation to UB (p = 0.041). The FB presented greater lactate concentration and induced slower heart rate variability recovery in relation to UB and LB conditions (p < 0.05), and heart rate variability remained lower until 60 minutes after exercise compared with rest only in the FB condition. There was a significant negative correlation between subjective hunger ratings and lactate concentration only for the FB condition (r = -0.72, p = 0.028). Full-body resistance exercise induced lower subjective hunger ratings after exercise in relation to UB resistance exercise. The FB also induced higher lactate production and slower recovery of autonomic modulation compared with the UB and LB conditions. Future research is necessary to investigate a mechanistic relationship between lactate concentrations and hunger suppression after resistance exercise.

Capsaicinoid and Capsinoids as an Ergogenic Aid: A Systematic Review and the Potential Mechanisms Involved.

CONTEXT: Capsaicinoids and capsinoids (CAP) are natural substances found primarily in chili peppers and other spicy foods that agonize the transient receptor potential vanilloid-1 in the mouth, stomach, and small intestine. Several studies have shown CAP to be a potential antiobesity agent and to exhibit an analgesic effect in both rodents and humans. However, there is no scientific consensus about the effects of CAP on physical exercise performance and its physiological mechanisms of action. PURPOSE: This systematic review aimed to better elucidate the effects of CAP compounds as ergogenic aids and to discuss underlying mechanisms of action by which this supplement may potentially enhance endurance performance and muscular strength. CONCLUSIONS: Among 22 studies included in the review, 14 examined the effects of capsaicinoid or capsinoid compounds on endurance and resistance exercise performance in animals, with 9 studies showing benefits on performance. In humans, 8 studies were included: 3 demonstrated significant acute endurance benefits and 2 showed acute resistance exercise performance benefits compared with a placebo condition. Therefore, while more mechanistic studies are necessary to confirm these outcomes in humans, the available scientific literature appears to suggest that these compounds could be considered an effective nutritional strategy to improve exercise performance.

Assessment of aerobic fitness in individuals with and without nonspecific chronic low back pain: a pilot study.

Aerobic fitness assessment in patients with low back pain (LBP) may help clinicians to plan how to progress the aerobic training. This was a pilot study designed to evaluate the performance of people with LBP on two different aerobic fitness tests performed on a treadmill and to compare the measure of aerobic fitness between people with LBP and healthy individuals. Ten people with LBP and 10 healthy individuals underwent two aerobic fitness protocols, the modified Bruce and maximum incremental test protocols, performed on a treadmill. Data collected during the protocols were: oxygen consumption, heart rate (HR), blood lactate concentration, respiratory quotient, rating of perceived exertion response, and pain intensity. Independent t-test and two-way analysis of variance were used respectively to assess difference between groups characteristics and physiological responses to the protocols. Our results showed that both groups were similar with regards to age (P = 0.839) or HRrest (P = 0.730) but the LBP group showed higher BMI compared to the healthy group (P = 0.031). Regarding the performance of both groups on the aerobic fitness tests, the only significant difference was reported for respiratory quotient which showed a main effect of test (P = 0.015) with higher values favoring the modified Bruce over the incremental test. Our study showed that most people with LBP are able to perform and tolerate both aerobic fitness tests but no significant differences between people with LBP and healthy individuals on both protocols were reported.