Prevalence of sarcopenic obesity according to different diagnostic methods and cut-off points in candidates for bariatric surgery.

BACKGROUND AND AIMS: Sarcopenic obesity (SO) is defined as a combination of low strength and muscle mass along with excess adiposity. Our study aimed to determine the prevalence of sarcopenic obesity in candidates for bariatric surgery, according to ESPEN/EASO criteria using bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). METHODS: Retrospective study of adult patients (18-60 years) candidates for bariatric surgery (BMI ≥40 kg/m2 or ≥35 kg/m2 with associated complications). Adiposity was assessed by the percentage of fat mass by DXA, according to Gallagher's cut-off points. Muscle strength was measured by hand grip according to Sánchez-Torralvo, Dodds, and <-2SD cut-off points of healthy reference population. Muscle mass was determined by DXA (ALM/weight according to Batsis) and by BIA (SMM/weight according to Janssen and according to reference population). In addition, the agreement of the different diagnostic methods of sarcopenic obesity was analyzed. RESULTS: A total of 124 subjects were included in the study, with 71.8 % being women. The overall mean age was 42.6 (SD 8.9) years. SO prevalence was found to be 13 %-22 % applying BIA with the SMM/weight equation according to Janssen, 14 %-23 % utilizing BIA with the SMM/weight equation according to the reference population, and 13 %-23 % employing DXA with the ALM/weight equation following Batsis criteria, depending on the specific hand grip strength cut-off points used. In general, we found good or very good concordances with the different diagnostic methods (with kappa values between 0.6 and 0.97). CONCLUSIONS: The prevalence of SO according to ESPEN/EASO criteria in candidates for bariatric surgery was 13 %-23 % based on the diagnostic method and cut-off points used.

Relación entre la Temperatura de Superficie, la Composición Corporal e Indicadores Antropométricos de Obesidad y Sobrepeso / Relationship Between Surface Temperature, Body Composition and Anthropometric Indicators of Obesity and Overweight

La termografía por infrarrojo (TI) permite evaluar la temperatura corporal, medir los cambios en la disipación del calor corporal en superficie y relacionarlos con las características de composición corporal e índices antropométricos. Aumentar el número de registros de zonas corporales evaluadas con TI y establecer las relaciones de estas temperaturas (32 áreas corporales) con variables de composición corporal e índices antropométricos, como el índice de masa corporal (IMC), índice cintura cadera, índice cintura estatura, en hombres adultos divididos según su estado ponderal. Participaron 60 hombres, adultos sanos, divididos en 2 grupos: grupo 1 (n=30), con IMC ≤ 24,9, edad 23,2 ± 3,9 años, masa corporal 66,5 ± 6,5 kg, y talla 170,5 ± 7,4 cm; y, grupo 2 (n= 30), con IMC > 24,9, edad 29,4 ± 9,9 años, masa corporal 84,5 ± 11,9 kg, y talla 172,0 ± 7,18 cm. Se realizaron evaluaciones antropométricas y de TI. Sujetos con IMC ≤ 24,9 kg/ m2 presentaron valores mayores de temperatura superficial, en todas las zonas estudiadas, a diferencia de los sujetos con niveles de IMC > 24,9 kg/m2, donde la disipación del calor corporal fue menor. Existe una estrecha relación entre la temperatura superficial de la piel y el IMC, donde sujetos con un IMC normal mostraron una disipación de calor y valores de temperatura superficial mayores, en todas las zonas evaluadas, a diferencia de los sujetos con un IMC que se encontraba por encima del límite de normalidad.

SUMMARY: Infrared thermography (IT) makes it possible to assess body temperature, measure changes in body heat dissipation on the surface, and relate them to body composition characteristics and anthropometric indices. The objective of this study was to increase the number of records of body areas evaluated with IT and establish the relationships of these temperatures (32 body areas) with body composition variables and anthropometric indices, such as body mass index (BMI), waist-hip ratio, waist-height ratio, in adult men divided according to their weight status. A total of 60 healthy adult men participated, divided into 2 groups: group 1 (n=30), with a body mass index (BMI) ≤ 24.9, age 23.2 ± 3.9 years, body mass 66.5 ± 6.5 kg, and height 170.5 ± 7.4 cm; and, group 2 (n = 30), with BMI > 24.9, age 29.4 ± 9.9 years, body mass 84.5 ± 11.9 kg, and height 172.0 ± 7.18 cm. Anthropometric and IT assessments were performed. Subjects with BMI ≤ 24.9 kg/ m2 presented higher values of surface temperature in all areas studied, unlike subjects with BMI levels > 24.9 kg/m2, where body heat dissipation was lower. There is a close relationship between skin surface temperature and BMI, where subjects with a normal BMI showed higher heat dissipation and surface temperature values, in all evaluated areas, unlike subjects with a BMI that was above the normal limit.

Influence of 12-Week Concurrent Training on Exosome Cargo and Its Relationship with Cardiometabolic Health Parameters in Men with Obesity.

Exosome release varies depending on the physiological state of the cell, so they could play a fundamental role in obesity, the biggest pandemic in today's societies. The beneficial effects that physical activity has both on weight and cardiovascular parameters may be mediated by exosomes released in response to exercise. Thus, we aimed (I) to study the influence of a 12-week CT intervention on exosome cargo modifications in men with obesity and (II) to determine whether changes in exosomes after the intervention were related to changes in cardiometabolic health parameters in our cohorts. An experimental, controlled design was performed in twelve (nine with valid data) adult male obese patients (mean values: 41.6 years old, 97.6 kg and 32.4 kg/m2) who were randomly divided into a control group (n = 4) and a training group (n = 5), which completed 36 sessions of CT (concurrent training) for 12 weeks. Before and after the training period, cardiometabolic health parameters were evaluated and blood samples to measure exosomes and proteins were drawn. No changes were observed in the levels of any exosomal markers and proteins; however, associations of changes between CD81 and both fat mass and weight, Flot-1 and VO2max, HSP70 and both CRP and left ventricle diastolic diameter or CD14 and leptin were found (all p ≤ 0.05). Although the current CT was not able to clearly modify the exosome cargo, a certain medium to large clinical effect was manifested considering the nature of this study. Moreover, the associations found between the promoted changes in cardiometabolic parameters and exosome-carried proteins could indicate a relationship to be considered for future treatments in patients with obesity.

Exercise Outcomes in Childhood Obesity-Related Inflammation and Oxidative Status.

Childhood obesity is identified as one of the major public health issues to increase the risk for cardiometabolic diseases and related complications in adulthood. The literature has supported inflammation and oxidative stress as the primary underlying mechanisms involved in the pathogenesis of obesity-related diseases. Epidemiological evidence consistently shows the benefits of physical activity in the improvement of obesity-mediated inflammation and oxidative stress status. In this narrative mini-review, the available scientific evidence on the potential effects of exercise in alleviating these susceptibilities in childhood obesity will be assessed.

Resistance Training Diminishes the Expression of Exosome CD63 Protein without Modification of Plasma miR-146a-5p and cfDNA in the Elderly.

Aging-associated inflammation is characterized by senescent cell-mediated secretion of high levels of inflammatory mediators, such as microRNA (miR)-146a. Moreover, a rise of circulating cell-free DNA (cfDNA) is also related to systemic inflammation and frailty in the elderly. Exosome-mediated cell-to-cell communication is fundamental in cellular senescence and aging. The plasma changes in exercise-promoted miR-146a-5p, cfDNA, and exosome release could be the key to facilitate intercellular communication and systemic adaptations to exercise in aging. Thirty-eight elderly subjects (28 trained and 10 controls) volunteered in an 8-week resistance training protocol. The levels of plasma miR-146a-5p, cfDNA, and exosome markers (CD9, CD14, CD63, CD81, Flotillin [Flot]-1, and VDAC1) were measured prior to and following training. Results showed no changes in plasma miR-146a-5p and cfDNA levels with training. The levels of exosome markers (Flot-1, CD9, and CD81) as well as exosome-carried proteins (CD14 and VDAC1) remained unchanged, whereas an attenuated CD63 response was found in the trained group compared to the controls. These findings might partially support the anti-inflammatory effect of resistance training in the elderly as evidenced by the diminishment of exosome CD63 protein expression, without modification of plasma miR-146a-5p and cfDNA.

Effects of exercise on exosome release and cargo in in vivo and ex vivo models: A systematic review.

Exercise-released exosomes have been identified as novel players to mediate cell-to-cell communication in promoting systemic beneficial effects. This review aimed to systematically investigate the effects of exercise on exosome release and cargo, as well as provide an overview of their physiological implications. Among the 436 articles obtained in the database search (WOS, Scopus, and PubMed), 19 articles were included based on eligibility criteria. Results indicate that exercise promotes the release of exosomes without modification of its vesicle size. The literature has primarily shown an exercise-driven increase in exosome markers (Alix, CD63, CD81, and Flot-1), along with other exosome-carried proteins, into circulation. However, exosome isolation, characterization, and phenotyping methodology, as well as timing of sample recovery following exercise can influence the analysis and interpretation of findings. Moreover, a large number of exosome-carried microRNAs (miRNAs), including miR-1, miR-133a, miR-133b, miR-206, and miR-486, in response to exercise are involved in the modulation of proliferation and differentiation of skeletal muscle tissue, although antigen-presenting cells, leukocytes, endothelial cells, and platelets are the main sources of exosome release into the circulation. Collectively, with the physiological implications as evidenced by the ex vivo trials, the release of exercise-promoted exosomes and their cargo could provide the potential therapeutic applications via the role of intercellular communication.

Exercise training modulates the gut microbiota profile and impairs inflammatory signaling pathways in obese children.

Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.

Aerobic Training Down-Regulates Pentraxin 3 and Pentraxin 3/Toll-Like Receptor 4 Ratio, Irrespective of Oxidative Stress Response, in Elderly Subjects.

Reactive oxygen and nitrogen species-mediated cellular aging has been linked to diseases such as atherothrombosis and cancer. Although pentraxin 3 (PTX3) is associated with aging-related diseases via TLR4-dependent anti-inflammatory effects, its relationship with oxidative stress in aging remains to be elucidated. Exercise is proposed as the key intervention for health maintenance in the elderly. This study aimed to examine the association of PTX3 levels with changes in oxidative stress in both plasma and peripheral blood mononuclear cells (PBMCs), following aerobic training in elderly adults. Nine trained and five controls participated in an eight-week aerobic training protocol. Enzyme-linked immunosorbent assay (ELISA) and Western blot analyses were used to determine PTX3, toll-like receptor 4 (TLR4), and levels of oxidative stress biomarkers [3-nitrotyrosine (3NT), 4-hydroxynonenal (4-HNE), reduced glutathione (GSH), protein carbonyl (PC), reactive oxygen/ nitrogen species (ROS/RNS), trolox equivalent antioxidant capacity (TEAC)] in plasma and/or PBMCs. Results showed a down-regulation of PTX3 expression in PBMCs following aerobic training, along with decreased PTX3/TLR4 ratios. Oxidative stress responses in PBMCs remained unchanged with the exercise protocol. Comparable levels of plasma PTX3 and oxidative stress biomarkers were observed in trained vs. control groups. No correlation was found between PTX3 and any oxidative stress biomarkers following training. These findings demonstrated the down-regulation of PTX3 and PTX3/TLR4 ratio, irrespective of oxidative stress response, in elderly adults following eight weeks of aerobic training.

Diclofenac attenuates inflammation through TLR4 pathway and improves exercise performance after exhaustive swimming.

BACKGROUND: The use of NSAIDs has become a common practice to counteract the pro-inflammatory acute effects of exercise, in order to improve sports performance. The liver, due to its central role in energy metabolism, may be involved primarily in the process of ROS generation and consequently inflammation after exhaustive exercise. OBJECTIVE: To analyze the influence of diclofenac on the liver TLR4 pathway and time to exhaustion in rats submitted to repeated exhaustive swimming. METHODS: An exhaustive test was performed in order to mimic athletes' routine, and inflammatory status and oxidative stress markers were evaluated in the liver. Animals were divided into sedentary and exhaustion groups, with this last performing three exhaustive swimming bouts. At the same time, diclofenac or saline was pre-administered once a day for nine days. RESULTS: Data showed significantly increased COX-2, TLR4, and MyD88 protein content in the liver after exhaustive swimming bouts. The levels of pro-inflammatory cytokines also increased after exhaustive exercise, while these effects were attenuated in the group treated with diclofenac plus exhaustive swimming bouts. The anti-inflammatory modulation provoked by diclofenac treatment was associated with an increased time to exhaustion in the exercise bouts. The exhaustive exercise increased TBARS formation, but diclofenac treatment blunted this elevation, while GSH/GSSG ratios in both exhaustion-saline and exhaustion-diclofenac-treated groups were lower than in the sedentary-saline group. CONCLUSIONS: Our findings suggest that diclofenac may improve exercise performance and represent an effective tool to ameliorate the pro-inflammatory status in liver when associated with exhaustive exercise, and the liver may be a possible therapeutic target.

Effects of a resistance-training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects.

Aging has been related with a decline in the ability to handle protein folding, which leads to endoplasmic reticulum stress and alterations in unfolded protein response (UPR). Importantly, physical activity could activate the UPR and attenuate or prevent age-induced endoplasmic reticulum (ER) dysfunction. The current study evaluated the effects of a resistance exercise on UPR and mitochondrial functions in peripheral blood mononuclear cells (PBMCs) from elderly subjects. Thirty healthy women and men (age, 72.8, sx- = 2.2 years) were randomized to a training group, which performed an 8-week resistance training programme, or a control group, which followed their daily routines. The phosphorylation of PERK and IRE1, as well as ATF4, and XBP1 protein expression, significantly increased following the training, while expression of BiP, AFT6 and CHOP remain without changes. Additionally, the intervention also induced an increase in PGC-1α and Mfn1 protein levels, while no changes were found in Drp1 expression. Finally, the resistance protocol was not able to activate PINK1/Parkin and Bnip3/Nix pathways. The results obtained seem to indicate that 8-week resistance exercise activates the UPR, stimulates mitochondrial biogenesis, maintains mitochondrial dynamics and prevents mitophagy activation by unfolded proteins in PBMCs from elderly subjects.

Endoplasmic Reticulum Unfolded Protein Response, Aging and Exercise: An Update.

The endoplasmic reticulum (ER) is a dynamic and multifunctional organelle responsible for protein biosynthesis, folding, assembly and modifications. Loss of protein folding regulation, which leads to unfolded or misfolded proteins accumulation inside the ER lumen, drives ER stress (ERS) and unfolded protein response (UPR) activation. During aging, there is a decline in the ability of the cell to handle protein folding, accumulation and aggregation, and the function of UPR is compromised. There is a progressive failure of the chaperoning systems and a decline in many of its components, so that the UPR activation cannot rescue the ERS. Physical activity has been proposed as a powerful tool against aged-related diseases, which are linked to ERS. Interventional studies have demonstrated that regular exercise is able to decrease oxidative stress and inflammation and reverse mitochondrial and ER dysfunctions. Exercise-induced metabolic stress could activate the UPR since muscle contraction is directly involved in its activation, mediating exercise-induced adaptation responses. In fact, regular moderate-intensity exercise-induced ERS acts as a protective mechanism against current and future stressors. However, biological responses vary according to exercise intensity and therefore induce different degrees of ERS and UPR activation. This article reviews the effects of aging and exercise on ERS and UPR, also analyzing possible changes induced by different types of exercise in elderly subjects.

Mitochondrial Function and Mitophagy in the Elderly: Effects of Exercise.

Aging is a natural, multifactorial and multiorganic phenomenon wherein there are gradual physiological and pathological changes over time. Aging has been associated with a decrease of autophagy capacity and mitochondrial functions, such as biogenesis, dynamics, and mitophagy. These processes are essential for the maintenance of mitochondrial structural integrity and, therefore, for cell life, since mitochondrial dysfunction leads to an impairment of energy metabolism and increased production of reactive oxygen species, which consequently trigger mechanisms of cellular senescence and apoptotic cell death. Moreover, reduced mitochondrial function can contribute to age-associated disease phenotypes in model organisms and humans. Literature data show beneficial effects of exercise on the impairment of mitochondrial biogenesis and dynamics and on the decrease in the mitophagic capacity associated to aging. Thus, exercise could have effects on the major cell signaling pathways that are involved in the mitochondria quality and quantity control in the elderly. Although it is known that several exercise protocols are able to modify the activity and turnover of mitochondria, further studies are necessary in order to better identify the mechanisms of interaction between mitochondrial functions, aging, and physical activity, as well as to analyze possible factors influencing these processes.

Previous physical exercise alters the hepatic profile of oxidative-inflammatory status and limits the secondary brain damage induced by severe traumatic brain injury in rats.

KEY POINTS: An early inflammatory response and oxidative stress are implicated in the signal transduction that alters both hepatic redox status and mitochondrial function after traumatic brain injury (TBI). Peripheral oxidative/inflammatory responses contribute to neuronal dysfunction after TBI Exercise training alters the profile of oxidative-inflammatory status in liver and protects against acute hyperglycaemia and a cerebral inflammatory response after TBI. Approaches such as exercise training, which attenuates neuronal damage after TBI, may have therapeutic potential through modulation of responses by metabolic organs. The vulnerability of the body to oxidative/inflammatory in TBI is significantly enhanced in sedentary compared to physically active counterparts. ABSTRACT: Although systemic responses have been described after traumatic brain injury (TBI), little is known regarding potential interactions between brain and peripheral organs after neuronal injury. Accordingly, we aimed to investigate whether a peripheral oxidative/inflammatory response contributes to neuronal dysfunction after TBI, as well as the prophylactic role of exercise training. Animals were submitted to fluid percussion injury after 6 weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha and ATP-binding cassette transporter, and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α and interleukin (IL)-6 expression per se in liver. Interestingly, exercise training protected against hepatic inflammation (COX-2, iNOS, TNF-α and IL-6), oxidative stress (decreases in non-protein sulfhydryl and glutathione, as well as increases in 2',7'-dichlorofluorescein diacetate oxidation and protein carbonyl), which altered hepatic redox status (increases in myeloperoxidase and superoxide dismutase activity, as well as inhibition of catalase activity) mitochondrial function (decreases in methyl-tetrazolium and Δψ, as well as inhibition of citrate synthase activity) and ion gradient homeostasis (inhibition of Na+ ,K+ -ATPase activity inhibition) when analysed 24 h after TBI. Previous exercise training also protected against dysglycaemia, impaired hepatic signalling (increase in phosphorylated c-Jun NH2-terminal kinase, phosphorylated decreases in insulin receptor substrate and phosphorylated AKT expression), high levels of circulating and neuronal cytokines, the opening of the blood-brain barrier, neutrophil infiltration and Na+ ,K+ -ATPase activity inhibition in the ipsilateral cortex after TBI. Moreover, the impairment of protein function, neurobehavioural (neuromotor dysfunction and spatial learning) disability and hippocampal cell damage in sedentary rats suggests that exercise training also modulates peripheral oxidative/inflammatory pathways in TBI, which corroborates the ever increasing evidence regarding health-related outcomes with respect to a physically active lifestyle.

Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects.

Aging is associated with a decline in autophagy and a state of low-grade inflammation which further affects apoptosis and autophagy. Importantly, these alterations could reverse with regular physical activity. This study assessed the effects of a resistance exercise training program on autophagy, NLRP3 inflammasome, and apoptosis in peripheral blood mononuclear cells (PBMCs) from old subjects. Twenty-six healthy women and men (age, 69.6±1.5 yr) were randomized to a training (TG) or a control (CG) group. TG performed an 8-week resistance training program, while CG followed their daily routines. Protein expression of beclin-1, Atg12, Atg16 and LAMP-2 increased following the training program, while expression of p62/SQSTM1 and phosphorylation of ULK-1 at Ser757 were significantly lower. Resistance exercise also induced a decrease in NLRP3 expression and in the caspase-1/procaspase-1 ratio. Expression of Bcl-2 and Bcl-xL, as well as the Bad/BcL-2 ratio were reduced, and there was a significant decrease in the protein content of caspase-3. The results obtained seem to indicate that 8-week resistance training stimulates autophagy, prevents NLRP3 inflammasome activation, and reduces apoptosis in PBMCs from elderly subjects. These data could have a significant impact in prevention and rehabilitation programs currently employed in elderly population.

Effects of aerobic training on markers of autophagy in the elderly.

Autophagy is a molecular process essential for the maintenance of cellular homeostasis, which appears to (i) decline with age and (ii) respond to physical exercise. In addition, recent evidence suggests a crosstalk between autophagy and toll-like receptor (TLR)-associated inflammatory responses. This study assessed the effects of aerobic exercise training on autophagy and TLR signaling in older subjects. Twenty-nine healthy women and men (age, 69.7 ± 1.0 year) were randomized to a training (TG) or a control (CG) group. TG performed an 8-week aerobic training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and protein levels of protein 1 light chain 3 (LC3), sequestosome 1 (p62/SQSTM1), beclin-1, phosphorylated unc-51-like kinase (ULK-1), ubiquitin-like autophagy-related (Atg)12, Atg16, and lysosome-associated membrane protein (LAMP)-2 were measured. TLR2 and TLR4 signaling pathways were also analyzed. Peak oxygen uptake increased in TG after the intervention. Protein expression of beclin-1, Atg12, Atg16, and the LC3II/I ratio increased following the training program (p < 0.05), while expression of p62/SQSTM1 and phosphorylation of ULK-1 at Ser(757) were lower (p < 0.05). Protein content of TLR2, TLR4, myeloid differentiation primary response gen 88 (MyD88), and TIR domain-containing adaptor-inducing interferon (TRIF) were not significantly modified by exercise. The current data indicate that aerobic exercise training induces alterations in multiple markers of autophagy, which seem to be unrelated to changes in TLR2 and TLR4 signaling pathways. These results expand knowledge on exercise-induced autophagy adaptations in humans and suggest that the exercise type employed may be a key factor explaining the potential relationship between autophagy and TLR pathways.

Whole-body vibration improves the anti-inflammatory status in elderly subjects through toll-like receptor 2 and 4 signaling pathways.

Regular physical exercise has anti-inflammatory effects in elderly subjects. Yet, the inflammatory responses after whole body vibration (WBV) training, a popular exercise paradigm for the elderly, remain to be elucidated. This study assessed the effects of WBV training on the inflammatory response associated with toll-like receptors (TLRs) signaling pathways. Twenty-eight subjects were randomized to a training group (TG) or a control group (CG). TG followed an 8-week WBV training program. Blood samples were obtained before and after the training period in both groups. Peripheral blood mononuclear cells were isolated, and mRNA and protein levels of makers involved in the TLR2/TLR4 myeloid differentiation primary response gen 88 (MyD88) and TIR domain-containing adaptor inducing interferon (TRIF)-dependent pathways were analyzed. Plasma TNFα and C-reactive protein levels were also assessed. The WBV program reduced protein expression of TLR2, TLR4, MyD88, p65, TRIF and heat shock protein (HSP) 60, while HSP70 content increased. IL-10 mRNA level and protein concentration were upregulated, and TNFα protein content decreased, after WBV training. Plasma concentration of C-reactive protein and TNFα decreased in the TG. The current data suggest WBV may improve the anti-inflammatory status of elderly subjects through an attenuation of MyD88- and TRIF-dependent TLRs signaling pathways.

Hypoxia-inducible factor-1 modulates the expression of vascular endothelial growth factor and endothelial nitric oxide synthase induced by eccentric exercise.

The present study investigated the effects of acute and chronic eccentric exercise on the hypoxia-inducible factor (HIF)-1α activation response and the concomitant modulation of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expression in rat skeletal muscle. Twenty-four male Wistar rats were randomly assigned to three experimental groups: rested control group, acutely exercised group after an intermittent downhill protocol for 90 min, and acutely exercise group with a previous eccentric training of 8 wk. HIF-1α activation, VEGF and eNOS gene expression, protein content, and promoter activation were assessed in vastus lateralis muscle biopsies. Acute eccentric exercise induced a marked activation of HIF-1α and resulted in increased VEGF and eNOS mRNA level and protein concentration. The binding of HIF-1α to the VEGF and eNOS promoters, measured by a chromatin immunoprecipitation assay, was undetectable in rested rats, whereas it was evident in acutely exercised animals. Acute exercise also increased myeloperoxidase, toll-like receptor-4, tumor necrosis factor-α, and interleukin-1ß protein content, suggesting a contribution of proinflammatory stimuli to HIF-1α activation and VEGF overexpression. All of these effects were partially abolished by training. Moreover, training resulted in an increased capillary density. In summary, our findings indicate that eccentric exercise prompts an HIF-1α response in untrained skeletal muscle that contributes to the upregulation of VEGF and eNOS gene expression and is attenuated after an eccentric training program.

Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects.

This study assessed the effects of a resistance exercise training program on the inflammatory response associated with Toll-like receptor (TLR) 2 and TLR4 signaling pathways in senior participants. Twenty-six healthy subjects (age, 69.5 ± 1.3) were randomized to a training (TG; n = 16) or a control (CG; n = 10) group. TG performed an 8-week resistance training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and levels of proteins involved in the TLR2, TLR4, and myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways were analyzed. The inflammatory status was evaluated through messenger RNA (mRNA) and protein content of interleukin (IL)-10 and tumor necrosis factor alpha (TNF-α) and plasma levels of C-reactive protein (CRP). After the 8-week resistance training, TLR2 and TLR4 protein expression was reduced in TG. MyD88, p65, phospho-p38, TIR domain-containing adaptor inducing interferon (TRIF), IKKi/IKKε, phospho-interferon regulatory factor (IRF) 3, and phosho-IRF7 were also downregulated in TG after the intervention. The training program induced an increase of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Hsp70 and a reduction of Hsp60. While TNF-α mRNA and protein values remained unchanged in both TG and CG, IL-10 mRNA and protein content were upregulated in TG after the intervention. CRP values decreased in TG only. The increase in Hsp70 negatively correlated with TLR2 and TLR4 downregulation. These data suggest that resistance exercise may represent an effective tool to ameliorate the pro-inflammatory status of old participants through an attenuation of MyD88-dependent and MyD88-independent TLR2 and TLR4 signaling pathways.

TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.

This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation of several nuclear transcription factors, such as nuclear factor κB (NF-κB), and interferon regulatory transcription factor 3 (IRF3), was analyzed. The inflammatory response after the first acute bout was similar between TG and CG, showing an upregulation of all the markers analyzed, with the exception of IRF3. After the second bout, the upregulation of TLR4 signaling pathway was blunted in TG, but not in CG, through both the myeloid differentiation factor 88- and toll/interleukin-1 receptor domain containing adapter inducing interferon-ß-dependent pathways. These results highlight the role of the TLR4 in controlling the exercise-induced inflammatory response in young women. More importantly, these data suggest eccentric training may help to prevent TLR4 activation principally through NF-κB, and perhaps IRF3, downstream signaling in this population.