Non-specific inhibition of dipeptidyl peptidases 8/9 by dipeptidyl peptidase 4 inhibitors negatively affects mesenchymal stem cell differentiation

DPP4 may play a relevant role in MSC differentiation into osteoblasts or adipocytes. Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4i), such as sitagliptin and vildagliptin, are used as antidiabetic drugs. However, vildagliptin is not a specific DPP4i and also inhibits DPP8/9, which is involved in energy metabolism and immune regulation. The aim of this study is to evaluate how sitagliptin, vildagliptin or 1G244 (a DPP8/9 specific inhibitor) may influence cell viability, as well as osteogenic and adipogenic differentiation in human mesenchymal stem cells (MSC). Viability, apoptosis, osteoblastogenesis and adipogenesis markers, as well as protein synthesis of β-catenin, were studied in MSC cultures induced to differentiate into osteoblasts or adipocytes in the presence or absence of sitagliptin, vildagliptin or 1G244. The two tested DPP4i did not affect MSC viability, but 1G244 significantly decreased it in MSC and osteoblast-induced cells. Additionally, 1G244 and vildagliptin inhibited osteogenesis and adipogenesis, unlike sitagliptin. Therefore, inhibition of DPP4 did not affect MSC viability and differentiation, whereas inhibition of DPP8/9 negatively affected MSC. To the best of our knowledge, these results show for the first time that DPP8/9 have an important role in the viability and differentiation of human MSC. This data can be considered for human clinical use of drugs affecting DPP8/9 activity

Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment

BackgroundObesity (OB) is a chronic metabolic disease with important associated comorbidities and mortality. Vitamin D supplementation is frequently administered after bariatric surgery (BS), so as to reduce OB-related complications, maybe including chronic inflammation.AimThis study aimed to explore relations between vitamin D metabolites and components of the inflammasome machinery in OB before and after BS and their relations with the improvement of metabolic comorbidities.Patients and methodsEpidemiological/clinical/anthropometric/biochemical evaluation was performed in patients with OB at baseline and 6 months after BS. Evaluation of i) vitamin-D metabolites in plasma and ii) components of the inflammasome machinery and inflammatory-associated factors [NOD-like-receptors (NLRs), inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators] in peripheral blood mononuclear cells (PBMCs) was performed at baseline and 6 months after BS. Clinical and molecular correlations/associations were analyzed.ResultsSignificant correlations between vitamin D metabolites and inflammasome-machinery components were observed at baseline, and these correlations were significantly reduced 6 months after BS in parallel to a decrease in inflammation markers, fat mass, and body weight. Treatment with calcifediol remarkably increased 25OHD levels, despite 24,25(OH)2D3 remained stable after BS. Several inflammasome-machinery components were associated with improvement in metabolic comorbidities, especially hypertension and dyslipidemia.ConclusionThe beneficial effects of vitamin D on OB-related comorbidities after BS patients are associated with significant changes in the molecular expression of key inflammasome-machinery components. The expression profile of these inflammasome components can be dynamically modulated in PBMCs after BS and vitamin D supplementation, suggesting that this profile could likely serve as a sensor and early predictor of the reversal of OB-related complications after BS

Effect of intermittent hypoxic conditioning on inflammatory biomarkers in older adults

Ageing is associated with chronic low-grade inflammation and with a decrease in muscle mass and strength. The aim of the study was to evaluate the effect of a resistance training programme in conditions of intermittent hypoxia on inflammatory biomarkers in older people. A total of 54 older adults (aged 65–75 years), who voluntarily participated in the study, were randomly divided into three groups: the control (CON) group, the resistance training normoxia (RTN) group that performed resistance training in normoxia and resistance training hypoxia (RTH) group that trained under hypoxic conditions at a simulated altitude of 2500 m above sea level. The training programme that was carried out during 24 weeks was similar in both experimental groups and consisted of a full-body workout with elastic bands and kettlebells (three sets x 12–15 reps). Blood inflammatory parameters (CRP, VCAM-1, IL-6, IL-8 and IL-10) were analysed before and after the intervention. After the resistance training programme, a significant decrease in CRP and IL-8 levels was observed, as well as an increase in IL-10 levels, both in normoxia and hypoxia. These results show that resistance training, either in conditions of normoxia or hypoxia, is useful to deal with the chronic inflammation associated with ageing.This study has been supported by the Government of Extremadura (Spain) with funding from the Regional Ministry of Economy and Infrastructures (Grant Ref.: IB18010) and from the European Regional Development Fund (Grant Ref: GR18003).peerReviewe

EFECTOS ENTRENAMIENTO INTERVÁLICO DE MÁXIMA INTENSIDAD EN HIPOXIA (EIMIH) SOBRE LA COMPOSICIÓN CORPORAL

Tradicionalmente, el entrenamiento en altura ha sido utilizado para mejorar el rendimiento de los deportistas. Con el desarrollo de nuevas tecnologías que permiten simular situaciones de altitud en cualquier parte del mundo, se han empezado a estudiar los efectos de la exposición a la misma en combinación con otros métodos de entrenamiento, por ejemplo, el entrenamiento interválico de máxima intensidad (Czuba et al. 2013) Por otra parte, recientemente se han llevado a cabo otros estudios que analizaron los efectos del estímulo hipóxico sobre los cambios en la composición corporal (Kaiser &amp; Verges, 2013).Objetivo: Combinar entrenamiento en altitud simulada y entrenamiento de máxima intensidad para analizar los efectos sobre la composición corporal en sujetos activos.<br /

Normobaric Hypoxia Exposure on Substrate Oxidation Pattern: Sex Differences.

Context. Hypoxic exposure has been associated with a metabolic perturbation that might affect basal energy expenditure (BEE). Objective. The aim was to examine the metabolic response during hypoxic exposure of men and women adults. Design. Crossover design with two experimental trials: normoxic and hypoxic exposure. Subjects and Methods. Twenty-nine healthy subjects (14 women) participated in (1) control study (NOR), subjected first to normoxic exposure (FiO2 = 20.9%) and (2) after that, to passive normobaric hypoxic exposure study (HYP) (FiO2 = 15%). Respiratory gases and blood glucose samples were recorded every hour in hypoxia chamber (8 points in total), and blood lactate samples were collected at baseline, at 4 and 7 h to exposure. Results. In females, basal energy expenditure was significantly higher at 2h, 4h, 6h and 7h compared with NOR group. Also, BEE was lower in females compared with men from 2h of hypoxia exposure. In the HYP group the blood lactate concentration increased significantly at 4h and 7 h relative to NOR group (P < 0.05) in males. Conclusion. An exposure to moderate normobaric hypoxia did not alter metabolic response, but induced a different response on substrate oxidation in adults men and women

High-Intensity Interval Training in Normobaric Hypoxia Leads to Greater Body Fat Loss in Overweight/Obese Women than High-Intensity Interval Training in Normoxia

A moderate hypoxic stimulus is considered a promising therapeutic modality for several pathological states including obesity. There is scientific evidence suggesting that when hypoxia and physical activity are combined, they could provide benefits for the obese population. The aim of the present study was to investigate if exposure to hypoxia combined with two different protocols of high-intensity interval exercise in overweight/obese women was more effective compared with exercise in normoxia. Study participants included 82 overweight/obese women, who started a 12 week program of 36 sessions, and were randomly divided into four groups: (1) aerobic interval training in hypoxia (AitH; FiO2 = 17.2%; n = 13), (2) aerobic interval training in normoxia (AitN; n = 15), (3) sprint interval training in hypoxia (SitH; n = 15), and (4) sprint interval training in normoxia (SitN; n = 18). Body mass, body mass index, percentage of total fat mass, muscle mass, basal metabolic rate, fat, and carbohydrate oxidation, and fat and carbohydrate energy were assessed. Outcomes were measured at baseline (T1), after 18 training sessions (T2), 7 days after the last session (T3), and 4 weeks after the last session (T4). The fat mass in the SitH group was significantly reduced compared with the SitN group from T1 to T3 (p < 0.05) and from T1 to T4 (p < 0.05) and muscle mass increased significantly from T1 to T4 (p < 0.05). Fat mass in the AitH group decreased significantly (p < 0.01) and muscle mass increased (p = 0.022) compared with the AitN group from T1 to T4. All training groups showed a reduction in the percentage of fat mass, with a statistically significant reduction in the hypoxia groups (p < 0.05). Muscle mass increased significantly in the hypoxia groups (p < 0.05), especially at T4. While fat oxidation tended to increase and oxidation of carbohydrates tended to decrease in both hypoxia groups, the tendency was reversed in the normoxia groups. Thus, high-intensity interval training under normobaric intermittent hypoxia for 12 weeks in overweight/obese women seems to be promising for reducing body fat content with a concomitant increase in muscle mass.(VLID)3081015Version of recor

Efectos entrenamiento interválico de máxima intensidad en hipoxia (EIMIH) sobre la composición corporal

Tradicionalmente, el entrenamiento en altura ha sido utilizado para mejorar el rendimiento de los deportistas. Con el desarrollo de nuevas tecnologías que permiten simular situaciones de altitud en cualquier parte del mundo, se han empezado a estudiar los efectos de la exposición a la misma en combinación con otros métodos de entrenamiento, por ejemplo, el entrenamiento interválico de máxima intensidad (Czuba et al., 2013). Por otra parte, recientemente se han llevado a cabo otros estudios que analizaron los efectos del estímulo hipóxico sobre los cambios en la composición corporal (Kaiser & Verges, 2013). Objetivo: Combinar entrenamiento en altitud simulada y entrenamiento de máxima intensidad para analizar los efectos sobre la composición corporal en sujetos activos.Traditionally, altitude training has been used to improve the performance of athletes. With the development of new technologies that allow to simulate situations of altitude in any part of the world, they have begun to study the effects of exposure to it in combination with other training methods, for example, maximum intensity interval training (Czuba et al., 2013). On the other hand, other studies have recently been carried out that analyzed the effects of the hypoxic stimulus on changes on body composition (Kaiser & Verges, 2013). Objective: To combine simulated altitude training and maximum intensity training to analyze the effects on body composition in active subjects.peerReviewe

Effects of Whole-Body Vibration Training Combined With Cyclic Hypoxia on Bone Mineral Density in Elderly People

Moderate intermittent hypoxia (IH) protocols may help to restrain osteoclastic activity and/or stimulate osteoblastic activity. Therefore, whole-body vibration (WBV) combined with IH exposure may provide the most effective treatment for osteoporosis. The present randomised controlled trial investigated if normobaric IH exposure combined with WBV training over an 18-week period for the elderly is more effective in increasing/maintaining bone mineral density when compared to WBV training or resting in normoxia. Healthy elderly persons (n=32) were randomly assigned to a: Hypoxia-Whole Body Vibration group (HWBV; n=10), Normoxic-Whole Body Vibration group (NWBV; n=11) or Control group (CON; n=10). The HWBV group performed WBV treatment under normobaric hypoxic conditions (16.1% FiO2). A vibration session included 4 bouts of 30 s (12.6 Hz in frequency and 4 mm in amplitude with 120º of knee flexion) with 1 min. rest between bouts. The NWBV group performed the same vibration treatment as the hypoxia group but under normoxic conditions. Proximal femur and whole body bone mineral density (BMD; g·cm-2) were measured using dual-energy X-ray absorptiometry. After 18 weeks, the HWBV group showed a significant 3.77% increment in BMD for the whole body (p<0.05) compared to those in the NWBV (-0.91%) and CON (0.97%) groups. In the analysis of the proximal femur, trochanter BMD in the HWVB group increased significantly (0.61%; p=0.05) compared to the CON group (-1.54%). The NWBV group had a significantly increased BMD of Trochanter (1.15%; p=0.037). Normobaric IH combined with WBV training improved BMD values in the whole body and proximal femur regions of the elderly more than the isolated WBV treatment

Sex‐specific dose–response effects of a 24‐week supervised concurrent exercise intervention on cardiorespiratory fitness and muscular strength in young adults : The ACTIBATE randomized controlled trial

Concurrent training has been postulated as an appropriate time-efficient strategy to improve physical fitness, yet whether the exercise-induced adaptations are similar in men and women is unknown. An unblinded randomized controlled trial was conducted to investigate sex-specific dose–response effects of a 24-week supervised concurrent exercise training program on cardiorespiratory fitness and muscular strength in young adults. One hundred and forty-four sedentary adults aged 18–25 years were assigned to either (i) a control group (n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 46), or (iii) a vigorous intensity exercise group (VIG-EX, n = 44) by unrestricted randomization. Cardiorespiratory fitness (VO2max), hand grip strength, and one-repetition maximum of leg press and bench press were evaluated at baseline and after the intervention. A total of 102 participants finished the intervention (Control, n = 36; 52% women, MOD-EX, n = 37; 70% women, and VIG-EX, n = 36; 72% women). In men, VO2max significantly increased in the MOD-EX (~8%) compared with the control group and in the VIG-EX group after the intervention (~6.5%). In women, VO2max increased in the MOD-EX and VIG-EX groups (~5.5%) compared with the control group after the intervention. There was a significant increment of leg press in the MOD-EX (~15.5%) and VIG-EX (~18%) groups compared with the control group (~1%) in women. A 24-week supervised concurrent exercise was effective at improving cardiorespiratory fitness and lower body limbs muscular strength in young women—independently of the predetermined intensity—while only at moderate intensity improved cardiorespiratory fitness in men.peerReviewe