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.

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.

Resistance Training Modulates Reticulum Endoplasmic Stress, Independent of Oxidative and Inflammatory Responses, in Elderly People.

Aging is related to changes in the redox status, low-grade inflammation, and decreased endoplasmic reticulum unfolded protein response (UPR). Exercise has been shown to regulate the inflammatory response, balance redox homeostasis, and ameliorate the UPR. This work aimed to investigate the effects of resistance training on changes in the UPR, oxidative status, and inflammatory responses in peripheral blood mononuclear cells of elderly subjects. Thirty elderly subjects volunteered to participate in an 8-week resistance training program, and 11 youth subjects were included for basal assessments. Klotho, heat shock protein 60 (HSP60), oxidative marker expression (catalase, glutathione, lipid peroxidation, nuclear factor erythroid 2-related factor 2, protein carbonyls, reactive oxygen species, and superoxide dismutase 1 and 2), the IRE1 arm of UPR, and TLR4/TRAF6/pIRAK1 pathway activation were evaluated before and following training. No changes in the HSP60 and Klotho protein content, oxidative status markers, and TLR4/TRAF6/pIRAK1 pathway activation were found with exercise. However, an attenuation of the reduced pIRE1/IRE1 ratio was observed following training. Systems biology analysis showed that a low number of proteins (RPS27A, SYVN1, HSPA5, and XBP1) are associated with IRE1, where XBP1 and RPS27A are essential nodes according to the centrality analysis. Additionally, a gene ontology analysis confirms that endoplasmic reticulum stress is a key mechanism modulated by IRE1. These findings might partially support the modulatory effect of resistance training on the endoplasmic reticulum in the elderly.

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.

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.

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.