Vascular Dynamics and Peripheral Oxygen Uptake in Obese Individuals during Progressive Physical Exercise.

BACKGROUND: Obese men show higher O2 consumption than lean men during physical exercise, with a trend toward higher peripheral O2 extraction; this is probably due to their larger muscle mass. OBJECTIVES: The aim of this study was to examine this phenomenon by measuring 2 vasoactive substances, endothelin-1 (ET-1) and nitric oxide (NO), during a progressive submaximal exercise. METHODS: Seventeen obese (body mass index [BMI] 38.6) and 15 lean (BMI 22.5) men performed a maximal progressive cycle ergometer exercise to determine peak power output (PPO) and peak O2 consumption (V∙O2peak); thereafter, they performed a submaximal cycle ergometer incremental test (every 6 min) at the same percentage of V∙O2peak until they reached 57.5% PPO. Blood samples were collected at rest and at the end of every step to measure ET-1 and NO concentrations. RESULTS: At rest, the ET-1 and NO concentrations in obese men and lean controls were the same. However, during exercise, the ET-1 concentration at each step was significantly lower (p < 0.05) in the obese group. There was no significant difference in NO concentration between the 2 groups, although the increase at the beginning of the exercise session was faster in obese individuals. During submaximal exercise, end-tidal O2 pressure (PETO2) was lower in the obese group, with a significant difference in the PETO2/fat-free mass ratio at each step. CONCLUSIONS: ET-1 and NO levels during physical exercise are different in obese versus lean men. This may support the notion that increased O2 consumption in obesity is due to different behaviors of the cardiorespiratory and circulatory systems.

Short bouts of anaerobic exercise increase non-esterified fatty acids release in obesity.

PURPOSE: It is demonstrated that aerobic exercise plays an important role in weight loss programs for obesity by increasing 24 h metabolic rate. While aerobic exercise can result in health and fitness benefits in obese subjects, also independently of weight loss, not completely clear are the effects of bouts of hard exercise on metabolic outcomes. The aim of this study was to test the hypothesis that short-term aerobic activity with anaerobic bouts might result in a greater improvement in the management of obesity than aerobic activity alone. METHODS: We studied 16 obese subjects (eight men) during a progressive cycloergometric test up to exhaustion, before and after 4 weeks of two different training schedules (6 days/week). Insulin and glycaemia, non-esterified fatty acids (NEFA) and lactic acid were sampled. Group A (eight subjects, four men) performed an aerobic cycle workout; Group B (eight subjects, four men) performed a 25 min aerobic workout followed by 5 min of anaerobic workout. All the subjects maintained their individual eating habits. RESULTS: The post-training test showed a decrease in AUCs NEFA in Group A (p < 0.05) and an increase in Group B (p < 0.05), together with an increase in lactic acid in Group A and a decrease in Group B (p < 0.01). ß-cell function (HOMA2-B) revealed a reduction only in Group A (p < 0.05). Group B achieved a greatest reduction in body fat mass than Group A (p < 0.05). CONCLUSIONS: Aerobic plus anaerobic training seem to produce a greater response in lipid metabolism and not significant modifications in glucose indexes; then, in training prescription for obesity, we might suggest at starting weight loss program aerobic with short bouts of anaerobic training to reduce fat mass and subsequently a prolonged aerobic training alone to ameliorate the metabolic profile.

On the generation of force required for actin-based motility.

The fundamental question of how forces are generated in a motile cell, a lamellipodium, and a comet tail is the subject of this note. It is now well established that cellular motility results from the polymerization of actin, the most abundant protein in eukaryotic cells, into an interconnected set of filaments. We portray this process in a continuum mechanics framework, claiming that polymerization promotes a mechanical swelling in a narrow zone around the nucleation loci, which ultimately results in cellular or bacterial motility. To this aim, a new paradigm in continuum multi-physics has been designed, departing from the well-known theory of Larché-Cahn chemo-transport-mechanics. In this note, we set up the theory of network growth and compare the outcomes of numerical simulations with experimental evidence.

Modeling Receptor Motility along Advecting Lipid Membranes.

This work aims to overview multiphysics mechanobiological computational models for receptor dynamics along advecting cell membranes. Continuum and statistical models of receptor motility are the two main modeling methodologies identified in reviewing the state of the art. Within the former modeling class, a further subdivision based on different biological purposes and processes of proteins' motion is recognized; cell adhesion, cell contractility, endocytosis, and receptor relocations on advecting membranes are the most relevant biological processes identified in which receptor motility is pivotal. Numerical and/or experimental methods and approaches are highlighted in the exposure of the reviewed works provided by the literature, pertinent to the topic of the present manuscript. With a main focus on the continuum models of receptor motility, we discuss appropriate multiphyisics laws to model the mass flux of receptor proteins in the reproduction of receptor relocation and recruitment along cell membranes to describe receptor-ligand chemical interactions, and the cell's structural response. The mass flux of receptor modeling is further supported by a discussion on the methodology utilized to evaluate the protein diffusion coefficient developed over the years.

Playing around the anaerobic threshold during COVID-19 pandemic: advantages and disadvantages of adding bouts of anaerobic work to aerobic activity in physical treatment of individuals with obesity.

INTRODUCTION: Obesity is a condition that generally limits work capacity and predisposes to a number of comorbidities and related diseases, the last being COVID-19 and its complications and sequelae. Physical exercise, together with diet, is a milestone in its management and rehabilitation, although there is still a debate on intensity and duration of training. Anaerobic threshold (AT) is a broad term often used either as ventilatory threshold or as lactate threshold, respectively, detected by respiratory ventilation and/or respiratory gases (VCO2 and VO2), and by blood lactic acid. AIMS AND METHODOLOGY: This review outlines the role of AT and of the different variations of growth hormone and catecholamine, in subjects with obesity vs normal weight individuals below and beyond AT, during a progressive increase in exercise training. We present a re-evaluation of the effects of physical activity on body mass and metabolism of individuals with obesity in light of potential benefits and pitfalls during COVID-19 pandemic. Comparison of a training program at moderate-intensity exercise (< AT) with training performed at moderate intensity (< AT) plus a final bout of high-intensity (> AT) exercise at the end of the aerobic session will be discussed. RESULTS: Based on our data and considerations, a tailored strategy for individuals with obesity concerning the most appropriate intensity of training in the context of rehabilitation is proposed, with special regard to potential benefits of work program above AT. CONCLUSION: Adding bouts of exercise above AT may improve lactic acid and H+ disposal and improve growth hormone. Long-term aerobic exercise may improve leptin reduction. In this way, the propensity of subjects with obesity to encounter a serious prognosis of COVID-19 may be counteracted and the systemic and cardiorespiratory sequelae that may ensue after COVID-19, can be overcome. Individuals with serious comorbidities associated with obesity should avoid excessive exercise intensity.

Dynamics of GH secretion during incremental exercise in obesity, before and after a short period of training at different work-loads.

BACKGROUND: Growth hormone (GH) secretion is normally sensitive to physical exercise. Intensity and duration of exercise, fitness and age can all influence the GH response to exercise. In obesity, GH secretion is decreased both in basal conditions and in response to exercise. OBJECTIVE: To analyse the dynamics of GH response to a progressive cycloergometric test, conducted up to exhaustion, in adult normal subjects and obese patients, after a reconditioning program at different workloads. DESIGN AND METHODS: We studied eight lean subjects (four men, mean age 34.3 years, range 26-47 years, mean body mass index (BMI) 22.1 kg/m(2)). GH was sampled at baseline and during the last 30 s of each power output increase. Anaerobic threshold (AT) was detected by the V-slope method. The same test was carried out in 16 obese subjects (seven men, mean age 39.1 years, range 20-59 years, mean BMI 35.8 kg/m(2)) and repeated after a 4-week reconditioning program consisting of aerobic workout (Group A, eight subjects, three men, mean age 40.5 years, range 22-59 years, mean BMI 33.6 kg/m(2)), and aerobic plus anaerobic work (group B, eight subjects, four men, mean age 37.6 years, range 20-56 years, mean BMI 38.0 kg/m(2)) for 6 days/week, with no dietary restrictions. RESULTS: Mean exercise peak occurred at higher intensity in controls (140 vs 110 W, P < 0.05), and AT exceeded at higher work outputs than in obese subjects (102 vs 74 W, P < 0.05). In controls, GH response to exercise was prompt and further sustained after AT; in obese subjects, GH increased slowly and insignificantly before AT, thereafter it increased to lower levels than in controls (P < 0.001). Following the reconditioning period, both Group A and Group B of obese subjects failed to improve exercise performance as well as GH response to exercise before AT; beyond AT, a greater GH response to exercise occurred in Group B than Group A (7.59 ± 0.32 µg/l at peak of exercise) with significantly different Delta AUCs (Area Under the Curves) following AT: 30.5 ± 12 µg.min/l in Group A vs 124.2 ± 38 µg.min/l in Group B, P < 0.05. CONCLUSIONS: Our results confirm the blunted GH response to exercise in obese adults when compared to lean counterparts. With obesity, aerobic training poorly increases the GH response beyond AT, while supplemental anaerobic workload appears to increase GH response beyond AT. These observations may have implications for the prescription of physical exercise, which is one of the recommendations in the management of obesity.

Ventilation and its control during incremental exercise in obesity.

BACKGROUND: In obesity, the addition of mass loading of the chest wall by adipose tissue decreases compliance, but its ventilation does not seem to be a limiting factor to physical performance. Plasma K(+) and lactic acid are considered important determinants of ventilation during exercise. Obesity is characterized by insulin resistance. OBJECTIVES: The aim of this study was to assess ventilatory adaptations to sustained effort and the effects of lactic acid and potassium in young obese subjects. METHODS: Twelve obese subjects with a body mass index of 40 (mean age 27 years, 6 males) and 12 normal subjects with a body mass index of 22 (aged 28 years, 6 males) performed a progressive cycloergometric test with increases of 20 W every 4 min to exhaustion while minute ventilation, oxygen consumption, carbon dioxide production, end-tidal oxygen pressure, and end-tidal carbon dioxide pressure were measured. Blood samples were collected at the end of every step to determine plasma K(+). Lactic acid was measured at rest, 40, 80, 120 W and peak exercise (or only at peak exercise if <120 W). Before each exercise, we tested insulin sensitivity using the quantitative insulin sensitivity check index. RESULTS: Obese subjects had lower insulin sensitivity (0.318 vs. 0.345, p < 0.01). Peak exercise was not significantly different between both groups (125 W in the obese group vs. 137 W in the control group), but the ventilatory threshold was at lower power output in the obese group compared to the controls (76 vs. 107 W, p < 0.05). Ventilation increased less in the obese group but oxygen saturation of hemoglobin remained within normal limits up to exhaustion in both groups. Ventilation was appropriate for the CO(2) increase but less appropriate for the increased O(2) consumption. Both K(+) and lactic acid increased less in the obese group. CONCLUSIONS: In our obese subjects, ventilation was not a limiting factor during exercise. Its lower increase may be due, in addition to the characteristics of their chest walls, to insulin resistance which may limit the increase in lactic acid during effort, and to the hypertrophy of muscle fibers previously noted, which may be linked to a lower increase in plasma K(+) during physical exercise.

Motor control exercises of the lumbar-pelvic region improve respiratory function in obese men. A pilot study.

PURPOSE: Obese subjects have decreased pulmonary function. The hypothesis of our study was that poor coordination of the lumbar-pelvic musculature secondary to obesity may hinder the synergic activation of the respiratory muscles. The aim of the paper was to evaluate whether specific motor control exercises of the lumbar-pelvic musculature were able to improve respiratory function. METHOD: Twenty obese male patients underwent a rehabilitation program including adapted physical activity and respiratory physiotherapy. Patients were randomly assigned to a Specific Motor Control Exercise Group (SG) and a Control Group (CG). SG followed a protocol according to the SMARTERehab concept aimed at improving posture, intra-abdominal pressure, rib cage mobility, and perception of correct muscle activation. CG performed an exercise training protocol to improve aerobic capacity and muscle strength. RESULT: After intervention, both groups showed similar changes in body weight, fat, and fat-free mass. Respiratory function indexes improved in SG due to improved proprioception and coordination of the deep lumbar-pelvic muscles. CONCLUSION: Our study provides preliminary evidence that breathing, postural control, and spinal stability are intertwined. Positive respiratory effects in obese men can be obtained by prescribing specific motor control exercises of the lumbar-pelvic muscles. Implications for rehabilitation Obese subjects present with decreased pulmonary function and postural changes. Poor coordination of the lumbar-pelvic muscles affects posture and the synergic activation of the respiratory muscles. Specific motor control exercises of the lumbar-pelvic musculature can improve respiratory function. Breathing and postural control are intertwined: positive respiratory effects can be obtained by enhancing motor control of the lumbar-pelvic muscles.

Multi-physics interactions drive VEGFR2 relocation on endothelial cells.

Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is a pro-angiogenic receptor, expressed on endothelial cells (ECs). Although biochemical pathways that follow the VEGFR2 activation are well established, knowledge about the dynamics of receptors on the plasma membrane remains limited. Ligand stimulation induces the polarization of ECs and the relocation of VEGFR2, either in cell protrusions or in the basal aspect in cells plated on ligand-enriched extracellular matrix (ECM). We develop a mathematical model in order to simulate the relocation of VEGFR2 on the cell membrane during the mechanical adhesion of cells onto a ligand-enriched substrate. Co-designing the in vitro experiments with the simulations allows identifying three phases of the receptor dynamics, which are controlled respectively by the high chemical reaction rate, by the mechanical deformation rate, and by the diffusion of free receptors on the membrane. The identification of the laws that regulate receptor polarization opens new perspectives toward developing innovative anti-angiogenic strategies through the modulation of EC activation.

The cortico-diaphragmatic pathway involvement in amyotrophic lateral sclerosis: neurophysiological, respiratory and clinical considerations.

Cortico-diaphragmatic pathway was investigated by means of transcranial magnetic stimulation (TMS), in 14 patients affected by definite amyotrophic lateral sclerosis (ALS) without clinical signs of respiratory impairment. Spirometry, gas analysis, and measurement of static inspiratory and expiratory pressures were performed in all patients. Forced vital capacity, forced expiratory volume at the first and second peak expiratory flow, sniff effort from FRC level (SNIP), maximal inspiratory and expiratory pressure at mouth (MIP/MEP), maximal transdiaphragmatic pressure (Pdimx) were considered. TMS was performed, recording by surface electrodes from hemidiaphragm, bilaterally. Latency of cortical and spinal motor-evoked potentials (Cx-MEP/Sp-MEP) and central motor conduction time (CMCT) were measured. None of the patients showed altered spirometry and gas levels. Seven patients showed decreased Pdimx and eight of MEP values. Four patients showed a delayed Sp-MEP. In one patient the Cx-MEP was abolished while the mean values of both Cx-MEP and CMCT were significantly increased (19.2+/-4.1 ms, P<0.0001; 10.8+/-4.8 ms, P<0.0001). Cx-MEP and CMCT did not show significant correlations with any of the respiratory measures. The patients with prolonged Sp-MEP, showed longer disease duration, lower Norris score, lower Pdimx and MEP values. In conclusion, cortico-diaphragmatic study is a sensitive measure to reveal subclinical diaphragmatic impairment although not correlated to respiratory measures.

Long maximal incremental tests accurately assess aerobic fitness in class II and III obese men.

This study aimed to compare two different maximal incremental tests with different time durations [a maximal incremental ramp test with a short time duration (8-12 min) (STest) and a maximal incremental test with a longer time duration (20-25 min) (LTest)] to investigate whether an LTest accurately assesses aerobic fitness in class II and III obese men. Twenty obese men (BMI≥35 kg.m-2) without secondary pathologies (mean±SE; 36.7±1.9 yr; 41.8±0.7 kg*m-2) completed an STest (warm-up: 40 W; increment: 20 W*min-1) and an LTest [warm-up: 20% of the peak power output (PPO) reached during the STest; increment: 10% PPO every 5 min until 70% PPO was reached or until the respiratory exchange ratio reached 1.0, followed by 15 W.min-1 until exhaustion] on a cycle-ergometer to assess the peak oxygen uptake [Formula: see text] and peak heart rate (HRpeak) of each test. There were no significant differences in [Formula: see text] (STest: 3.1±0.1 L*min-1; LTest: 3.0±0.1 L*min-1) and HRpeak (STest: 174±4 bpm; LTest: 173±4 bpm) between the two tests. Bland-Altman plot analyses showed good agreement and Pearson product-moment and intra-class correlation coefficients showed a strong correlation between [Formula: see text] (r=0.81 for both; p≤0.001) and HRpeak (r=0.95 for both; p≤0.001) during both tests. [Formula: see text] and HRpeak assessments were not compromised by test duration in class II and III obese men. Therefore, we suggest that the LTest is a feasible test that accurately assesses aerobic fitness and may allow for the exercise intensity prescription and individualization that will lead to improved therapeutic approaches in treating obesity and severe obesity.

Short-term HIIT and Fat max training increase aerobic and metabolic fitness in men with class II and III obesity.

OBJECTIVE: To compare the effects of two different 2-week-long training modalities [continuous at the intensity eliciting the maximal fat oxidation (Fatmax) versus high-intensity interval training (HIIT)] in men with class II and III obesity. METHODS: Nineteen men with obesity (BMI ≥ 35 kg · m(-2)) were assigned to Fatmax group (GFatmax) or to HIIT group (GHIIT). Both groups performed eight cycling sessions matched for mechanical work. Aerobic fitness and fat oxidation rates (FORs) during exercise were assessed prior and following the training. Blood samples were drawn to determine hormones and plasma metabolites levels. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA2-IR). RESULTS: Aerobic fitness and FORs during exercise were significantly increased in both groups after training (P ≤ 0.001). HOMA2-IR was significantly reduced only for GFatmax (P ≤ 0.001). Resting non-esterified fatty acids (NEFA) and insulin decreased significantly only in GFatmax (P ≤ 0.002). CONCLUSIONS: Two weeks of HIIT and Fatmax training are effective for the improvement of aerobic fitness and FORs during exercise in these classes of obesity. The decreased levels of resting NEFA only in GFatmax may be involved in the decreased insulin resistance only in this group.

Fat oxidation, hormonal and plasma metabolite kinetics during a submaximal incremental test in lean and obese adults.

This study aimed to compare fat oxidation, hormonal and plasma metabolite kinetics during exercise in lean (L) and obese (O) men. Sixteen L and 16 O men [Body Mass Index (BMI): 22.9 ± 0.3 and 39.0 ± 1.4 kg · m(-2)] performed a submaximal incremental test (Incr) on a cycle-ergometer. Fat oxidation rates (FORs) were determined using indirect calorimetry. A sinusoidal model, including 3 independent variables (dilatation, symmetry, translation), was used to describe fat oxidation kinetics and determine the intensity (Fat(max)) eliciting maximal fat oxidation. Blood samples were drawn for the hormonal and plasma metabolite determination at each step of Incr. FORs (mg · FFM(-1) · min(-1)) were significantly higher from 20 to 30% of peak oxygen uptake (VO2peak) in O than in L and from 65 to 85% VO2peak in L than in O (p ≤ 0.05). FORs were similar in O and in L from 35 to 60% VO2peak. Fat max was 17% significantly lower in O than in L (p<0.01). Fat oxidation kinetics were characterized by similar translation, significantly lower dilatation and left-shift symmetry in O compared with L (p<0.05). During whole exercise, a blunted lipolysis was found in O [lower glycerol/fat mass (FM) in O than in L (p ≤ 0.001)], likely associated with higher insulin concentrations in O than in L (p<0.01). Non-esterified fatty acids (NEFA) were significantly higher in O compared with L (p<0.05). Despite the blunted lipolysis, O presented higher NEFA availability, likely due to larger amounts of FM. Therefore, a lower Fat(max), a left-shifted and less dilated curve and a lower reliance on fat oxidation at high exercise intensities suggest that the difference in the fat oxidation kinetics is likely linked to impaired muscular capacity to oxidize NEFA in O. These results may have important implications for the appropriate exercise intensity prescription in training programs designed to optimize fat oxidation in O.

Kinetics of catecholamines and potassium, and heart rate during exercise testing in obese subjects. Heart rate regulation in obesity during exercise.

BACKGROUND: Obesity is characterised by a marked insulin resistance which involves an abnormal regulation of K(+) uptake and metabolism. Less is known about the effect of physical exercise on K(+) kinetics. AIM OF THE STUDY: To assess plasma catecholamines and potassium levels and their relationship with cardiac activity during a physical effort up to exhaustion in young obese subjects. METHODS: Blood samples for epinephrine (E), norepinephrine (NE), potassium (K+) and heart rate (HR) were collected at the end of every step during a progressive cycloergometric test up to exhaustion in twelve obese subjects (6 males, aged 26+/-2, BMI 39.9+/-1) and twelve normal subjects (6 males, aged 28.2+/-2, BMI 22+/-1). In every subject anaerobic threshold (AT) was detected. RESULTS: In obese subjects plasma catecholamines rose faster but had a lower peak in correspondence of maximal work-loads, with respect to controls. Catecholamines had a linear correlation in the obese group and a quadratic one in the control group when plotted vs O(2) consumption. The increase of plasma potassium was less in obesity than in control. CONCLUSIONS: During physical exercise K(+) and catecholamines kinetics differ significantly in obese subjects vs normals and they may justify a less prompt cardiac response at the higher work-loads and a lower work capacity. The present data can be interpreted in the light of the insulin resistance syndrome of obesity, which causes an abnormal regulation of the Na-KATPase and of K(+) channels during physical exercise. The results of the present study may be relevant to nutritionists when suggesting physical exercise to obese subjects.

Lung function and methacholine responsiveness among adolescents in an air-polluted area.

BACKGROUND: Outdoor air pollution is hazardous to human pulmonary health. Airway inflammation is an important cause of bronchial hyperresponsiveness. Information is not univocal about the potential effects of prolonged exposure to environmental air pollutants on lung function. OBJECTIVES: A cross-sectional study was performed to assess bronchial responsiveness to methacholine in children living in an air-polluted area. Afterwards, the same study protocol was repeated in children of similar age living in mountain valleys with virtually no air pollution. METHODS: Every child underwent a lung function test, skin tests to common allergens, total serum levels of IgE, and a challenge to methacholine at increasing doses (PD20 FEV1). Subjects were 246 children 11-12 years old living in an air-polluted area, and 285 children 11-13 years old living in mountain valleys. Respectively, 156 and 161 were negative to skin tests and had serum total IgE<100 IU/ml, and had no asthma or other recurrent or ongoing respiratory symptoms. RESULTS: Lung function data, adjusted for the effect of potential confounders showed significantly lower FVC, and even more so FEV1, in the children from the polluted area. After the exclusion of subjects with positive skin tests and serum total IgE>100 IU/ml and those with history of asthma or respiratory disorders, there were higher percentages of positive responses in the challenge to methacholine in children from the polluted area (28.9 vs. 15.5%, p<0.001). CONCLUSIONS: These data may corroborate the possible importance of long exposure to air pollutants on the prevalence of bronchial aspecific hyperresponsiveness in otherwise normal children.