Strength gain through eccentric isotonic training without changes in clinical signs or blood markers.

BACKGROUND: Localized exercises are widely used in rehabilitation processes. The predominant options are exercises with an emphasis on either concentric or eccentric contractions. Eccentric exercises promote greater strength gains compared to classical concentric stimuli, but can cause muscle damage. The aim of present study was to compare strength training composed of 10 sessions with progressive loads between groups with a predominance of concentric versus eccentric contraction through an analysis of isotonic strength, pressure pain threshold, creatine kinase, tumor necrosis factor-alpha and cortisol. METHODS: One hundred twenty male subjects were divided into four groups: C1 and E1--single session of maximum strength with emphasis on concentric and eccentric contraction, respectively; C10 and E10--10 sessions with progressive loads from 80% to maximum strength with emphasis on concentric and eccentric contraction, respectively. RESULTS: Isotonic strength increased by 10% in E10 following the ten training sessions. C1 and E1 exhibited a lower pressure pain threshold 48 hours after the sessions in comparison to C10 and E10, respectively. Creatine kinase was increased in C1 in comparison to baseline, with significant differences (p ≤ 0.05) in comparison to E1 at 48 and 96 hours as well as C10 at 48, 72 and 96 hours. No significant differences were found in TNF-α or cortisol among the groups or evaluation times. CONCLUSION: Eccentric contraction training promotes functional adaptation. Moreover, both concentric and eccentric contraction training have a protective effect on the muscle in relation to a single session of maximum strength exercise. TRIAL REGISTRATION: RBR-75scwh.

Central obesity is detrimental to anti-inflammatory, phenotype, and exhaustion markers in mononuclear cells - A cross-sectional study.

OBJECTIVE: To investigate the role of central obesity on immunometabolic response in peripheral blood mononuclear cells (PBMCs) from normal weight and overweight/obese young men. METHODS: Eighteen individuals were classified as normal weight (NW; n = 9 - age: 25 ± 5 and BMI: 21.4 ± 1.7) and overweight/obese (OW; n = 9 - age: 29 ± 7 and BMI: 29.2 ± 2.7). The body composition was evaluated by dual-energy x-ray absorptiometry (DXA), waist circumference, and visceral and subcutaneous fat depots by ultrasound. Physical activity levels, metabolic parameters, immune phenotypic characterization, cytokine production by lipopolysaccharide (LPS) -stimulated whole blood cells and LPS or phorbol 12-myristate 13-acetate (PMA)-stimulated PBMC, and mitochondrial respiration in PBMCs were evaluated. Expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR-4), hypoxia-inducible factor-1 alpha (HIF-1α), and adrenergic receptor beta 1 and 2 (AR-ß1 and ß2) genes were evaluated in cultured PBMC using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Individuals with overweight/obese (OW) presented higher glucose (P = 0.009) and leptin (P = 0.010) than individuals with normal weight (NW). PBMCs of OW under stimulation with LPS presented a lower production of interleukin-10 (IL-10) (P = 0.011) and macrophage inflammatory protein-1alpha (MIP-1α) (P = 0.048) than NW. Mitochondrial respiration rates were not different between NW and OW subjects. Cultured PBMCs in LPS-stimulated condition indicated higher gene expression of AR-ß2 in OW, while PMA-stimulated PBMCs presented lower expression of AMPK (P = 0.002) and higher expression of NF-κB (P=<0.0001) than NW. OW presented higher numbers of CD3+CD4+ T cells (P = 0.009) and higher expression of programmed cell death protein 1 (PD-1) in CD8+ T cells (P = 0.001) than NW. CONCLUSION: Central obesity promoted reductions in interleukin 10 production response and increase in AR-ß2 expressions in mitogen-stimulated PBMCs. Furthermore, central obesity altered the phenotype of PBMCs, also increasing the expression of PD-1 exhaustion markers in young adults.

Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.

Lack of lymphocytes impairs macrophage polarization and angiogenesis in diabetic wound healing.

AIMS: This study aimed to investigate the effect of lymphocytes in wound healing and the underlying mechanisms, in diabetic and non-diabetic mice, using Balb/c recombination activating gene (Rag)-2 and interleukin 2 receptor gamma (IL-2Rγ) double knockout (KO) (RAG2-/- IL-2Rγ-/-) mice. MAIN METHODS: Wound healing in vivo was performed in control and STZ-induced diabetic mice, in both KO and WT mice. Inflammation and ROS production were evaluated by immunofluorescence microscopy analysis, antioxidant enzymes and angiogenesis were evaluated by quantitative PCR and immunofluorescence microscopy analysis, and wound closure kinetics evolution was evaluated by measurement of acetate tracing of the wound area. KEY FINDINGS: Wound closure was significantly delayed in KO mice, where the M1/M2 macrophage ratio and basal ROS levels were significantly increased, while antioxidant defenses and angiogenesis were significantly decreased. Moreover, the expected increase in matrix metallopeptidase (MMP)-9 protein levels in diabetic conditions was not observed in KO mice, suggesting that the mechanisms leading to the increase in MMP-9 observed in diabetic wounds may in part be lymphocyte-dependent. SIGNIFICANCE: Our results indicate that lack of lymphocytes compromises wound healing independent of diabetes. The lack of these cells, even in non-diabetic mice, mimics the phenotype observed in wounds under diabetic conditions. Moreover, the combination of diabetes and the lack of lymphocytes, further impair the wound healing conditions, indicating that when the innate regulatory function is lost in these KO mice, excessive M1 polarization, poor angiogenesis and impaired wound healing are worsen.

A Chemiresistor Sensor Based on Azo-Polymer and Graphene for Real-Time Monitoring of Mitochondrial Oxygen Consumption.

In the present study, a chemiresistor sensor based on a poly(Bismarck Brown Y)-reduced graphene oxide nanocomposite was developed to analyze the respiratory capacity of the constituent complexes of the electron transport chain. The sensorial platform was characterized using electrochemical impedance spectroscopy, and oxygen detection was accomplished by measuring the resistive properties of the sensor at fixed AC frequency. The impedance decreased significantly in response to small variations of the O2 concentrations tested up to saturation of the electrolyte solution with molecular oxygen. The resistive response of the sensor at 0.1 Hz was linear over the oxygen concentration range from 1.17 × 10-5 mol L-1 to 1.02 × 10-3 mol L-1, with a detection limit of 3.60 × 10-7 mol L-1. Using the new O2 sensing platform, we monitored gradients in static cultures of adherent cells exposed to graded oxygen both at rest and upon metabolic stimulation. Under high dissolved oxygen conditions, the respiration of resting cells dictated that local O2 was moderately reduced, while cell metabolic stimulation triggered a major redistribution of O2. The usefulness of the developed sensor was demonstrated by continuous monitoring of mitochondrial oxygen consumption in various biologic applications.

Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression.

Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2a4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2a4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (~30%) Slc2a4 mRNA and GLUT4 protein content; and increased (~30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (~50%) the Slc2a4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2a4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum- and inflammatory-stress and repression of Slc2a4/GLUT4 expression.

[Glucose transporters in the metabolic syndrome]. / Transportadores de glicose na síndrome metabólica.

Intra- and extra-cellular glucose homeostasis is directly related to gene expression control of different isoforms, which encode different glucose transporters, being tissue-specifically expressed, as a consequence of transcriptional factors activity of each gene, in each cellular type. The metabolic syndrome (MS) comprises a wide range of physiopathological abnormalities, all involved in systemic changes, which occur in different territories of the body, where glucose transporters changes are observed in diverse degrees. The present review will describe the glucose transporters expression changes clearly shown in literature, which reflexes in glucose flow, and can facilitate the MS physiopathological understanding, as well as possible treatments for the syndrome.

Calorie restriction reduces pinealectomy-induced insulin resistance by improving GLUT4 gene expression and its translocation to the plasma membrane.

The present study aimed to investigate insulin sensitivity and GLUT4 expression protein in pinealectomized rats, as well as to determining the effects of melatonin and calorie restriction on the changes induced by pinealectomy. Wistar rats were pinealectomized (Pinx) or sham operated (Sham), and studied 30 days later. Melatonin replacement treatment (50 g/100 g body weight) was continued for 30 days after pinealectomy. Calorie restriction was performed by offering 60% of the standard food intake. In vivo insulin sensitivity was evaluated using the glucose disappearance constant (kITT) during an insulin tolerance test, and GLUT4 mRNA and protein were assessed by Northern and Western blotting, respectively. The in vitro effect of melatonin on GLUT4 protein content in plasma membrane was investigated in adipocytes isolated from intact rats. Compared with Sham rats, Pinx rats showed decreased kITT (40%), GLUT4 expression in white adipose tissue (WAT, approximately 70%), and unchanged GLUT4 expression in skeletal muscle. Melatonin treatment in Pinx rats restored the kITT and GLUT4 protein to control values. No in vitro effects of melatonin (10-9 m) upon GLUT4 protein were observed. Calorie restriction of Pinx rats increased their kITT value ( approximately 40%), total GLUT4 protein content ( approximately 240%) and its translocation to the plasma membrane ( approximately 80%) in WAT. The results show that pinealectomy, for lack of melatonin, decreased insulin sensitivity as well as GLUT4 gene expression. Calorie restriction improved insulin sensitivity in Pinx rats, and this was related to increased GLUT4 gene expression and insulin-induced GLUT4 translocation to the plasma membrane in WAT.

Transportadores de glicose na síndrome metabólica / Glucose transporters in the metabolic syndrome

A regulação da homeostasia intra e extra-celular da glicose está diretamente relacionada ao controle preciso da expressão dos genes que codificam as diferentes isoformas de proteínas transportadoras de glicose, as quais se expressam de maneira tecido-específica, em conseqüência do padrão de ativação dos fatores transcricionais reguladores de cada gene, em cada tipo celular. A síndrome metabólica (SM) abrange uma grande variedade de alterações fisiopatológicas, todas de repercussões sistêmicas, acometendo os mais distintos territórios do organismo, nos quais alterações nos transportadores de glicose presentes são observadas em maior ou menor grau. A presente revisão abordará as alterações na expressão de transportadores de glicose claramente demonstradas na literatura, cujas repercussões nos fluxos territoriais de glicose auxiliam na compreensão de mecanismos fisiopatológicos da SM, assim como dos tratamentos propostos para esta entidade.

Intra- and extra-cellular glucose homeostasis is directly related to gene expression control of different isoforms, which encode different glucose transporters, being tissue-specifically expressed, as a consequence of transcriptional factors activity of each gene, in each cellular type. The metabolic syndrome (MS) comprises a wide range of physiopathological abnormalities, all involved in systemic changes, which occur in different territories of the body, where glucose transporters changes are observed in diverse degrees. The present review will describe the glucose transporters expression changes clearly shown in literature, which reflexes in glucose flow, and can facilitate the MS physiopathological understanding, as well as possible treatments for the syndrome.