Impact of continuous vs. interval training on oxygen extraction and cardiac function during exercise in type 2 diabetes mellitus.

PURPOSE: Exercise training improves exercise capacity in type 2 diabetes mellitus (T2DM). It remains to be elucidated whether such improvements result from cardiac or peripheral muscular adaptations, and whether these are intensity dependent. METHODS: 27 patients with T2DM [without known cardiovascular disease (CVD)] were randomized to high-intensity interval training (HIIT, n = 15) or moderate-intensity endurance training (MIT, n = 12) for 24 weeks (3 sessions/week). Exercise echocardiography was applied to investigate cardiac output (CO) and oxygen (O2) extraction during exercise, while exercise capacity [([Formula: see text] (mL/kg/min)] was examined via cardiopulmonary exercise testing at baseline and after 12 and 24 weeks of exercise training, respectively. Changes in glycaemic control (HbA1c and glucose tolerance), lipid profile and body composition were also evaluated. RESULTS: 19 patients completed 24 weeks of HIIT (n = 10, 66 ± 11 years) or MIT (n = 9, 61 ± 5 years). HIIT and MIT similarly improved glucose tolerance (pTime = 0.001, pInteraction > 0.05), [Formula: see text] (mL/kg/min) (pTime = 0.001, pInteraction > 0.05), and exercise performance (Wpeak) (pTime < 0.001, pInteraction > 0.05). O2 extraction increased to a greater extent after 24 weeks of MIT (56.5%, p1 = 0.009, pTime = 0.001, pInteraction = 0.007). CO and left ventricular longitudinal strain (LS) during exercise remained unchanged (pTime > 0.05). A reduction in HbA1c was correlated with absolute changes in LS after 12 weeks of MIT (r = - 0.792, p = 0.019, LS at rest) or HIIT (r = - 0.782, p = 0.038, LS at peak exercise). CONCLUSION: In patients with well-controlled T2DM, MIT and HIIT improved exercise capacity, mainly resulting from increments in O2 extraction capacity, rather than changes in cardiac output. In particular, MIT seemed highly effective to generate these peripheral adaptations. TRIAL REGISTRATION: NCT03299790, initially released 09/12/2017.

The Role of Skeletal Muscle Mitochondria in Colorectal Cancer Related Cachexia: Friends or Foes?

Up to 60% of colorectal cancer (CRC) patients develop cachexia. The presence of CRC related cachexia is associated with more adverse events during systemic therapy, leading to a high mortality rate. The main manifestation in CRC related cachexia is the loss of skeletal muscle mass, resulting from an imbalance between skeletal muscle protein synthesis and protein degradation. In CRC related cachexia, systemic inflammation, oxidative stress, and proteolytic systems lead to mitochondrial dysfunction, resulting in an imbalanced skeletal muscle metabolism. Mitochondria fulfill an important function in muscle maintenance. Thus, preservation of the skeletal muscle mitochondrial homeostasis may contribute to prevent the loss of muscle mass. However, it remains elusive whether mitochondria play a benign or malignant role in the development of cancer cachexia. This review summarizes current (mostly preclinical) evidence about the role of skeletal muscle mitochondria in the development of CRC related cachexia. Future human research is necessary to determine the physiological role of skeletal muscle mitochondria in the development of human CRC related cachexia.

Prolyl Carboxypeptidase Activity Is Present in Human Adipose Tissue and Is Elevated in Serum of Obese Men with Type 2 Diabetes.

Prolyl carboxypeptidase (PRCP) is involved in metabolic disorders by hydrolyzing anorexigenic peptides. A link between serum PRCP activity and obesity has been reported, but its origin/source is still unclear. Previously proven correlations between human serum PRCP activity and the amount of adipose tissue may suggest that adipose tissue is an important source of circulating PRCP. We investigated PRCP activity in visceral, subcutaneous adipose tissue (VAT and SCAT), skeletal muscle tissue and serum of lean and obese men with or without type 2 diabetes (T2D). Correlations between PRCP activity, metabolic and biochemical parameters and immune cell populations were assessed. PRCP activity was the highest in VAT, compared to SCAT, and was very low in skeletal muscle tissue in the overall group. Serum PRCP activity was significantly higher in T2-diabetic obese men, compared to lean and obese non-diabetic men, and was positively correlated with glycemic control. A positive correlation was observed between serum PRCP activity and VAT immune cell populations, which might indicate that circulating PRCP activity is deriving rather from the immune fraction than from adipocytes. In conclusion, PRCP activity was observed in human adipose tissue for the first time and serum PRCP activity is correlated with T2D in obese men.

Impact of Exercise Modalities on Peripheral and Central Components of Cardiorespiratory Capacity in Heart Transplantation Patients: A Systematic Review and Meta-Analysis.

Background and Objectives: To analyze the effects of aerobic, resistance, and combined training on peripheral and central components related to cardiorespiratory capacity after HTx. Materials and Methods: No time restriction was applied for study inclusion. MEDLINE/PubMed; EMBASE, CENTRAL, and PEDro databases were investigated. Studies reporting heart transplanted patients older than 19 years following aerobic, resistance, and combined training according. The outcomes included: V'O2 peak, VE/V'CO2 slope, heart rate (HR peak), systolic and diastolic blood pressure (SBP and DBP peak), maximum repetition test(1RM), sit-to-stand test, and flow-mediated dilation (FMD). The studies were selected by consensus. Four hundred ninety-two studies initially met the selection criteria. Cochrane handbook was used for abstracting data and assessing data quality and validity. Independent extraction by two observers was applied. Results: Isolated aerobic training leads to a greater increase in V'O2 peak than combined training compared to the control group (p < 0.001, I2 = 0%). However, no significant differences were found in the subgroup comparison (p = 0.19, I2 = 42.1%). HR peak increased similarly after aerobic and combined training. High-intensity interval training (HIIT) was better than moderate continuous intensity to increase the V'O2 after long term in HTx. Still, there is scarce evidence of HIIT on muscle strength and FMD. No change on VE/V'CO2 slope, FMD, and SBP, DBP peak. 1RM and the sit-to-stand test increased after resistance training (p < 0.001, I2 = 70%) and CT (p < 0.001, I2 = 0%) when compared to control. Conclusions: Aerobic and combined training effectively improve VO2 peak and muscle strength, respectively. HIIT seems the better choice for cardiorespiratory capacity improvements. More studies are needed to examine the impact of training modalities on VE/V'CO2 slope and FMD.

Cardiac function in adolescents with obesity: cardiometabolic risk factors and impact on physical fitness.

OBJECTIVE: To gain greater insights in the etiology and clinical consequences of altered cardiac function in obese adolescents. Therefore, we aimed to examine cardiac structure and function in obese adolescents, and to examine associations between altered cardiac function/structure and cardiometabolic disease risk factors or cardiopulmonary exercise capacity. METHODS: In 29 obese (BMI 31.6 ± 4.2 kg/m², age 13.4 ± 1.1 years) and 29 lean (BMI 19.5 ± 2.4 kg/m², age 14.0 ± 1.5 years) adolescents, fasted blood samples were collected to study hematology, biochemistry, liver function, glycemic control, lipid profile, and hormones, followed by a transthoracic echocardiography to assess cardiac structure/function, and a cardiopulmonary exercise test (CPET) to assess cardiopulmonary exercise parameters. Regression analyses were applied to examine relations between altered echocardiographic parameters and blood parameters or CPET parameters in the entire group. RESULTS: In obese adolescents, left ventricular septum thickness, left atrial diameter, mitral A-wave velocity, E/e' ratio were significantly elevated (p < 0.05), as opposed to lean controls, while mitral e'-wave velocity was significantly lowered (p < 0.01). Elevated homeostatic model assessment of insulin resistance and blood insulin, c-reactive protein, and uric acid concentrations (all significantly elevated in obese adolescents) were independent risk factors for an altered cardiac diastolic function (p < 0.01). An altered cardiac diastolic function was not related to exercise tolerance but to a delayed heart rate recovery (HRR; p < 0.01). CONCLUSIONS: In obese adolescents, an altered cardiac diastolic function was independently related to hyperinsulinemia and whole-body insulin resistance, and only revealed by a delayed HRR during CPET. This indicates that both hyperinsulinemia, whole-body insulin resistance, and delayed HRR could be regarded as clinically relevant outcome parameters.

Adrenergically and non-adrenergically mediated human adipose tissue lipolysis during acute exercise and exercise training.

Obesity-related adipose tissue (AT) dysfunction, in particular subcutaneous AT (SCAT) lipolysis, is characterized by catecholamine resistance and impaired atrial natriuretic peptide (ANP) responsiveness. It remains unknown whether exercise training improves (non-)adrenergically mediated lipolysis in metabolically compromised conditions. We investigated the effects of local combined α-/ß-adrenoceptor blockade on abdominal SCAT lipolysis in lean insulin sensitive (IS) (n=10), obese IS (n=10), and obese insulin resistant (IR) (n=10) men. Obese men participated in a 12-week exercise training intervention to determine the effects on SCAT lipolysis. Abdominal SCAT extracellular glycerol concentration and blood flow (ATBF) were investigated using microdialysis, with/without locally combined α-/ß-adrenoceptor blockade at rest, during low-intensity endurance-type exercise and post-exercise recovery. In obese IR men, microdialysis was repeated after exercise intervention. The exercise-induced increase in SCAT extracellular glycerol was more pronounced in obese IS compared with lean IS men, possibly resulting from lower ATBF in obese IS men. The exercise-induced increase in extracellular glycerol was blunted in obese IR compared with obese IS men, despite comparable local ATBF. Abdominal SCAT extracellular glycerol was markedly reduced (remaining ~60% of exercise-induced SCAT extracellular glycerol) following the local α-/ß-adrenoceptor blockade in obese IS but not in IR men, suggesting reduced catecholamine-mediated lipolysis during exercise in obese IR men. Exercise training did not affect (non-)adrenergically mediated lipolysis in obese IR men. Our findings showed a major contribution of non-adrenergically-mediated lipolysis during exercise in male abdominal SCAT. Furthermore, catecholamine-mediated lipolysis may be blunted during exercise in obese IR men but could not be improved by exercise intervention, despite an improved metabolic profile and body composition.

Attenuated atrial natriuretic peptide-mediated lipolysis in subcutaneous adipocytes of obese type 2 diabetic men.

Catecholamines and atrial natriuretic peptide (ANP) are major regulators of adipocyte lipolysis. Although obesity is characterized by catecholamine resistance in subcutaneous adipose tissue (SCAT), data on ANP lipolytic response and sensitivity in different adipose tissue (AT) depots of metabolically distinct humans are scarce. Ex vivo catecholamine- and ANP-induced lipolysis was investigated in adipocytes derived from SCAT and visceral AT (VAT) depot of lean (n=13) and obese men, with (n=11) or without (n=18) type 2 diabetes (HbA1c < or ≥ 6.5%). Underlying molecular mechanisms were examined by looking at functional receptors in the NP signalling pathway at the mRNA and protein level. Maximal ANP- and catecholamine-induced lipolysis in SCAT was blunted in obese type 2 diabetics compared with age-matched lean men whereas non-diabetic obese subjects showed intermediate responses. This blunted ANP-mediated lipolytic response was accompanied by lower mRNA and protein expression of the type-A natriuretic peptide (NP) receptor and higher mRNA but reduced protein expression of the scavenging type-C receptor. Maximal ANP-induced lipolysis was lower in VAT compared with SCAT but not different between groups. Collectively, our data show that both ANP- and catecholamine-mediated lipolysis is attenuated in SCAT of obese men with type 2 diabetes, and might be partially explained by NP receptor defects. Therefore, improving maximal ANP responsiveness in adipose tissue might be a potential novel strategy to improve obesity-associated metabolic complications.

Magnitude of muscle wasting early after on-pump coronary artery bypass graft surgery and exploration of aetiology.

NEW FINDINGS: What is the central question of this study? It remains uncertain whether significant fat-free mass wasting occurs early after coronary artery bypass graft surgery, and the aetiology of this wasting in these particular conditions is unexplored. What is the main finding and its importance? Significant fat-free mass wasting is present after coronary artery bypass graft surgery, and this wasting effect is greater in younger patients and in patients with greater increments in blood cortisol-to-testosterone ratios after surgery. The magnitude and aetiology of muscle wasting early after coronary artery bypass graft (CABG) surgery remains unknown. In the present study, we assessed changes in fat-free mass early after CABG surgery and explored the possible aetiology (relationships with postsurgical changes in blood hormones, insulin resistance, subject characteristics and inflammation) for these changes. Fat-free mass was assessed before and 23 (range: 25) days after CABG surgery in 25 subjects. Blood testosterone, cortisol, insulin-like growth factor-1, growth hormone, sex hormone-binding globulin, glucose, insulin, C-peptide and C-reactive protein concentrations were determined, and free androgen index, cortisol-to-testosterone ratio and HOMA-IR index were all calculated before surgery, during the first 3 days after surgery and at reassessment of body composition. Relationships between changes in fat-free mass and changes in blood parameters after surgery or subject characteristics were studied. After surgery, free androgen index and blood sex hormone-binding globulin, testosterone and insulin-like growth factor-1 concentrations decreased significantly, while HOMA-IR index, cortisol-to-testosterone ratio, blood growth hormone, insulin and C-reactive protein concentrations increased significantly (P < 0.0025, observed α > 0.80). Whole-body fat-free mass decreased significantly [by -1.9 (range: 9.1) kg, P < 0.0025, observed α = 0.99] after surgery. According to regression analysis, greater absolute loss of fat-free mass was observed after CABG surgery in subjects who were younger, who experienced a greater increase in blood cortisol-to-testosterone ratio after surgery and/or who underwent earlier reassessment of body composition (P < 0.05). Significant decrements in fat-free mass were observed early after CABG surgery, especially in younger subjects and/or subjects with elevated blood cortisol-to-testosterone ratios after surgery. Interventions to preserve fat-free mass soon after CABG surgery are thus warranted.

Accurate Prediction Equations for Ventilatory Thresholds in Cardiometabolic Disease When Gas Exchange Analysis is Unavailable: Development and Validation.

AIMS: To develop and validate equations predicting heart rate (HR) at the first and second ventilatory thresholds (VTs) and an optimized range-adjusted prescription for patients with cardiometabolic disease (CMD). To compare their performance against guideline-based exercise intensity domains. METHODS: Cross-sectional study involving 2,868 CMD patients from nine countries. HR predictive equations for first and second VTs (VT1, VT2) were developed using multivariate linear regression with 975 cycle-ergometer cardiopulmonary exercise tests (CPET). 'Adjusted' percentages of peak HR (%HRpeak) and HR reserve (%HRR) were derived from this group. External validation with 1,893 CPET (cycle-ergometer or treadmill) assessed accuracy, agreement, and reliability against guideline-based %HRpeak and %HRR prescriptions using mean absolute percentage error (MAPE), Bland-Altman analyses, intraclass correlation coefficients (ICC). RESULTS: HR predictive equations (R²: 0.77 VT1, 0.88 VT2) and adjusted %HRR (VT1: 42%, VT2: 77%) were developed. External validation demonstrated superiority over widely used guideline-directed intensity domains for %HRpeak and %HRR. The new methods showed consistent performance across both VTs with lower MAPE (VT1: 7.1%, VT2: 5.0%), 'good' ICC for VT1 (0.81, 0.82) and 'excellent' for VT2 (0.93). Guideline-based exercise intensity domains had higher MAPE (VT1: 6.8%-21.3%, VT2: 5.1%-16.7%), 'poor' to 'good' ICC for VT1, and 'poor' to 'excellent' for VT2, indicating inconsistencies related to specific VTs across guidelines. CONCLUSION: Developed and validated HR predictive equations and the optimized %HRR for CMD patients for determining VT1 and VT2 outperformed the guideline-based exercise intensity domains and showed ergometer interchangeability. They offer a superior alternative for prescribing moderate intensity exercise when CPET is unavailable.

Equations to predict heart rate at ventilatory thresholds were developed and externally validated, offering a new perspective when a cardiopulmonary exercise test is unavailable to accurately determine the aerobic exercise intensity domains. Additionally, an adjusted range for exercise intensity prescription based on the percentage of heart rate reserve (%HRR) was provided, utilizing a large sample from eight countries. The proposed equations and the range-adjusted %HRR significantly outperformed the guideline-directed methods for determining exercise intensity, exhibiting higher accuracy, agreement, and reliability. Exercise intensity prescription based on the percentage of heart rate peak showed higher errors, raising concerns about its clinical applicability. Our study may enhance the efficacy of exercise training and physical activity advice when gas exchange analysis is unavailable, potentially leading to improved clinical outcomes, even in low-resource settings. Employing these approaches in research could facilitate more tailored and consistent interventions, introducing a contemporary perspective for studies comparing exercise intensity prescriptions.

Chronotropic incompetence is more frequent in obese adolescents and relates to systemic inflammation and exercise intolerance.

BACKGROUND: Adults with obesity may display disturbed cardiac chronotropic responses during cardiopulmonary exercise testing, which relates to poor cardiometabolic health and an increased risk for adverse cardiovascular events. It is unknown whether cardiac chronotropic incompetence (CI) during maximal exercise is already present in obese adolescents and, if so, how that relates to cardiometabolic health. METHODS: Sixty-nine obese adolescents (body mass index standard deviation score = 2.23 ± 0.32, age = 14.1 ± 1.2 years; mean ± SD) and 29 lean adolescents (body mass index standard deviation score = -0.16 ± 0.84, age = 14.0 ± 1.5 years) performed a maximal cardiopulmonary exercise testing from which indicators for peak performance were determined. The resting heart rate and peak heart rate were used to calculate the maximal chronotropic response index. Biochemistry (lipid profile, glycemic control, inflammation, and leptin) was studied in fasted blood samples and during an oral glucose tolerance test within obese adolescents. Regression analyses were applied to examine associations between the presence of CI and blood or exercise capacity parameters, respectively, within obese adolescents. RESULTS: CI was prevalent in 32 out of 69 obese adolescents (46%) and 3 out of 29 lean adolescents (10%). C-reactive protein was significantly higher in obese adolescents with CI compared to obese adolescents without CI (p = 0.012). Furthermore, peak oxygen uptake and peak cycling power output were significantly reduced (p < 0.05) in obese adolescents with CI vs. obese adolescents without CI. The chronotropic index was independently related to blood total cholesterol (standardized coefficient ß = -0.332; p = 0.012) and C-reactive protein concentration (standardized coefficient ß = -0.269; p = 0.039). CONCLUSION: CI is more common in the current cohort of obese adolescents, and is related to systemic inflammation and exercise intolerance.

Extensive profiling of histidine-containing dipeptides reveals species- and tissue-specific distribution and metabolism in mice, rats, and humans.

AIM: Histidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules with potent antioxidative and carbonyl quenching properties linked to various inflammatory, metabolic, and neurological diseases, as well as exercise performance. However, the distribution and metabolism of HCDs across tissues and species are still unclear. METHODS: Using a sensitive UHPLC-MS/MS approach and an optimized quantification method, we performed a systematic and extensive profiling of HCDs in the mouse, rat, and human body (in n = 26, n = 25, and n = 19 tissues, respectively). RESULTS: Our data show that tissue HCD levels are uniquely produced by carnosine synthase (CARNS1), an enzyme that was preferentially expressed by fast-twitch skeletal muscle fibres and brain oligodendrocytes. Cardiac HCD levels are remarkably low compared to other excitable tissues. Carnosine is unstable in human plasma, but is preferentially transported within red blood cells in humans but not rodents. The low abundant carnosine analogue N-acetylcarnosine is the most stable plasma HCD, and is enriched in human skeletal muscles. Here, N-acetylcarnosine is continuously secreted into the circulation, which is further induced by acute exercise in a myokine-like fashion. CONCLUSION: Collectively, we provide a novel basis to unravel tissue-specific, paracrine, and endocrine roles of HCDs in human health and disease.

Muscle-Skeletal Abnormalities and Muscle Oxygenation during Isokinetic Strength Exercise in Heart Failure with Preserved Ejection Fraction Phenotype: A Cross-Sectional Study.

Exercise intolerance, a hallmark of patients with heart failure (HF), is associated with muscle weakness. However, its causative microcirculatory and muscle characteristics among those with preserved or reduced ejection fraction (HFpEF or HFrEF) phenotype is unclear. The musculoskeletal abnormalities that could result in impaired peripheral microcirculation are sarcopenia and muscle strength reduction in HF, implying lowered oxidative capacity and perfusion affect transport and oxygen utilization during exercise, an essential task from the microvascular muscle function. Besides that, skeletal muscle microcirculatory abnormalities have also been associated with exercise intolerance in HF patients who also present skeletal muscle myopathy. This cross-sectional study aimed to compare the muscle microcirculation dynamics via near-infrared spectroscopy (NIRS) response during an isokinetic muscle strength test and ultrasound-derived parameters (echo intensity was rectus femoris muscle, while the muscle thickness parameter was measured on rectus femoris and quadriceps femoris) in heart failure patients with HFpEF and HFrEF phenotypes and different functional severities (Weber Class A, B, and C). Twenty-eight aged-matched patients with HFpEF (n = 16) and HFrEF (n = 12) were assessed. We found phenotype differences among those with Weber C severity, with HFrEF patients reaching lower oxyhemoglobin (O2Hb, µM) (-10.9 ± 3.8 vs. -23.7 ± 5.7, p = 0.029) during exercise, while HFpEF reached lower O2Hb during the recovery period (-3.0 ± 3.4 vs. 5.9 ± 2.8, p = 0.007). HFpEF with Weber Class C also presented a higher echo intensity than HFrEF patients (29.7 ± 8.4 vs. 15.1 ± 6.8, p = 0.017) among the ultrasound-derived variables. Our preliminary study revealed more pronounced impairments in local microcirculatory dynamics in HFpEF vs. HFrEF patients during a muscle strength exercise, combined with muscle-skeletal abnormalities detected via ultrasound imaging, which may help explain the commonly observed exercise intolerance in HFpEF patients.

Exercise capacity is related to attenuated responses in oxygen extraction and left ventricular longitudinal strain in asymptomatic type 2 diabetes patients.

AIMS: Type 2 diabetes mellitus (T2DM) is associated with reduced exercise capacity and cardiovascular diseases, both increasing morbidity and risk for premature death. As exercise intolerance often relates to cardiac dysfunction, it remains to be elucidated to what extent such an interplay occurs in T2DM patients without overt cardiovascular diseases. Design: Cross-sectional study, NCT03299790. METHODS AND RESULTS: Fifty-three T2DM patients underwent exercise echocardiography (semi-supine bicycle) with combined ergospirometry. Cardiac output (CO), left ventricular longitudinal strain (LS), oxygen uptake (O2), and oxygen (O2) extraction were assessed simultaneously at rest, low-intensity exercise, and high-intensity exercise. Glycaemic control and lipid profile were assessed in the fasted state. Participants were assigned according to their exercise capacity being adequate or impaired (EXadequate: O2peak <80% and EXimpaired: O2peak ≥80% of predicted O2peak) to compare O2 extraction, CO, and LS at all stages. Thirty-eight participants (EXimpaired: n = 20 and EXadequate: n = 18) were included in the analyses. Groups were similar regarding HbA1c, age, and sex (P > 0.05). At rest, CO was similar in the EXimpaired group vs. EXadequate group (5.1 ± 1 L/min vs. 4.6 ± 1.4 L/min, P > 0.05) and increased equally during exercise. EXimpaired patients displayed a 30.7% smaller increase in O2 extraction during exercise compared to the EXadequate group (P = 0.016) which resulted in a lower O2 extraction at high-intensity exercise (12.5 ± 2.8 mL/dL vs. 15.3 ± 3.9 mL/dL, P = 0.012). Left ventricular longitudinal strain was similar at rest but increased significantly less in the EXimpaired vs. EXadequate patients (1.9 ± 2.5% vs. 5.9 ± 4.1%, P = 0.004). CONCLUSIONS: In asymptomatic T2DM patients, an impaired exercise capacity is associated with an impaired response in oxygen extraction and myocardial deformation (LS). TRIAL REGISTRY: Effect of High-intensity Interval Training on Cardiac Function and Regulation of Glycemic Control in Diabetic Cardiomyopathy (https://clinicaltrials.gov/ct2/show/NCT03299790).

Critical Reappraisal of the Role and Importance of Exercise Intervention in the Treatment of Obesity in Adults.

In the treatment of obesity in adults, exercise intervention is recommended and some people with obesity even prefer exercise above dietary intervention as a single weight-loss strategy. However, evidence is accumulating that the long-term body weight and adipose tissue mass loss ​as a result of exercise intervention in these individuals is disappointingly small. Although this could be related to various clinical reasons, more recent evidence reveals that also (patho)physiological abnormalities are involved which cannot be remediated by exercise intervention, especially in metabolically compromised patients. As a result, the role and importance of exercise intervention in the treatment of obesity deserve significant reconsideration to avoid confusion and disappointment amongst clinicians, patients and society. Hence, to reduce adipose tissue mass and body weight, dietary intervention is much more effective than exercise intervention, and is, therefore, of key importance in this endeavour. However, dietary interventions must be supplemented by exercise training to induce clinically relevant changes in specific cardiovascular or metabolic risk factors like blood pressure, blood triglycerides and high-density lipoprotein cholesterol concentrations, as well as visceral adipose tissue mass, physical fitness, muscle mass and strength, quality of life and life expectancy. This allows individuals with obesity to preserve their cardiometabolic health or to shift from a metabolically unhealthy phenotype to a metabolically healthy phenotype. Signifying the true clinical value of exercise interventions might lead to a better understanding and appreciation of the goals and associated effects when implemented in the multidisciplinary treatment of obesity, for which a proper tailoring of exercise prescription is required.

Aberrant Mechanical Efficiency during Exercise Relates to Metabolic Health and Exercise Intolerance in Adolescents with Obesity.

BACKGROUND: Mechanical efficiency (ME) might be an important parameter evaluating cardiometabolic health and the effectiveness of physical activity interventions in individuals with obesity. However, whether these cardiometabolic risk factors may relate to ME in adolescents with obesity is not known yet. Therefore, this study aims to compare the mechanical efficiency during maximal exercise testing between adolescents with obesity and lean adolescents, and to examine associations with exercise tolerance and metabolic health. METHODS: Twenty-nine adolescents with obesity (BMI SDS: 2.11 ± 0.32, age: 13.4 ± 1.1 years, male/female: 15/14) and 29 lean (BMI SDS: -0.16 ± 0.84, age: 14.0 ± 1.5 years, male/female: 16/13) adolescents performed a maximal cardiopulmonary exercise test from which the net mechanical efficiency (MEnet) and substrate oxidation (carbohydrates and lipids) were calculated. Indicators for peak performance were collected. Biochemistry (lipid profile, glycaemic control, inflammation, leptin) was studied in fasted blood samples. Regression analyses were applied to examine relations between MEnet and exercise tolerance or blood variables in the total group. RESULTS: Peak work rate (WRpeak), oxygen uptake (V˙O2peak)/WRpeak, ME, and MEnet were significantly lower (p < 0.05) in adolescents with obesity compared to their lean counterparts (p < 0.05). Furthermore, a reduced MEnet was independently related to a lower WRpeak (SC ß = 2.447; p < 0.001) and elevated carbohydrate oxidation during exercise (SC ß = -0.497; p < 0.001), as well as to elevated blood low-density lipoprotein cholesterol (SC ß = -0.275; p = 0.034) and fasting glucose (SC ß = -0.256; p = 0.049) concentration. CONCLUSION: In adolescents with obesity, the mechanical efficiency is lowered during exercise and this relates to exercise intolerance and a worse metabolic health.

Periodized versus classic exercise therapy in Multiple Sclerosis: a randomized controlled trial.

BACKGROUND: Periodizing exercise interventions in Multiple Sclerosis (MS) shows good high intensity exercise training adherence. Whether this approach induces comparable training adaptations with respect to exercise capacity, body composition and muscle strength compared to conventional, linear progressive training programs however is not known. METHODS: Thirty-one persons with MS (all phenotypes, mean EDSS 2.3±1.3) were randomized into a twelve-week periodized (MSPER, n=17) or a classic endurance (MSCLA, n=14) training program. At baseline (PRE), exercise capacity (maximal exercise test, VO2max), body composition (DEXA) and muscle strength (Biodex®) were assessed. Classic, moderate intensity endurance training (60-80% HRmax, 5 training sessions/2w, 60min/session) was performed on a stationary bicycle. Periodized exercise included 4 recurrent 3-week cycles of alternated endurance training (week 1: endurance training as described above), high intense exercise (week 2: 3 sessions/w, 3 × 20s all-out sprints, 10min/session) and recovery weeks (week 3: one sprint session as described above). POST measurements were performed similar to baseline. Total exercise volume of both programs was expressed as total peak-effort training minutes. RESULTS: For MSCLA, total exercise volume included 1728 total peak-effort training minutes, whereas MSPER included only 736. Despite this substantially reduced training volume, twelve weeks of periodized training significantly (p<0.05) improved VO2max (+14%, p=0.001), workload (+20%) and time until exhaustion (+25%). Classic training significantly (p<0.05) improved workload (+10%) and time until exhaustion (+17%), but not VO2max (+5%, p=0.131). Pre-post improvements for VO2max were significantly higher in MSPER compared to MSCLA (p=0.046). CONCLUSION: These data show that despite substantially lower training time (57% less peak-effort training minutes), 12 weeks of periodized exercise training in persons with MS seems to induce larger improvements in parameters of exercise capacity compared to classic endurance training. We therefore recommend to further investigate the effect of training periodization on various functional rehabilitation measures in MS.

High-intensity interval training versus progressive high-intensity circuit resistance training on endothelial function and cardiorespiratory fitness in heart failure: A preliminary randomized controlled trial.

INTRODUCTION: Exercise training is strongly recommended as a therapeutic approach to treat individuals with heart failure. High-intensity exercise training modalities still controversial in this population. The study aims to preliminary assess the consequences of high-intensity exercise training modalities, aerobic interval training (HIIT) and progressive high circuit-resistance training (CRT), on primarily endothelial function and cardiorespiratory fitness, and secondly on muscle strength and physical performance in heart failure patients. METHODS: This preliminary multicentric randomized controlled trial comprised 23 heart failure patients, aged 56 ± 10 years old, mainly New York Heart Association classification I and II (%), hemodynamically stable, who compromise at least 36 exercise sessions of a randomly assigned intervention (HIIT, CRT or control group). Endothelial function, cardiopulmonary exercise testing, muscle strength and physical performance were completed at baseline and post-intervention. RESULTS: Although no effects on endothelial function; both HIIT and CRT modalities were able to produce a positive effect on [Formula: see text] peak (HIIT = +2.1±6.5, CRT = +3.0±4.2 and control group = -0.1± 5.3 mL/kg/min, time*group p-value<0,05) and METs (HIIT = +0.6±1.8, CRT = +0.9±1.2 and control group = 0±1.6, time*group p-value<0,05). Only HIIT increased isokinetic torque peak (HIIT = +8.8±55.8, CRT = 0.0±60.7 and control group = 1.6±57.6 Nm) matched p-value<0,05. Regarding the physical performance, the CRT modality reduced chair stand test completion time (HIIT = -0.7±3.1, CRT = -3.3±3.2 and control group = -0.3±2.5 s, matched p-value<0,05 and HIIT improved global physical performance(time*group p<0,05). CONCLUSION: This preliminary study trends to indicate for the first time that high-intensity interval training promotes a jointly superior effect compared to progressive high intensity circuit-resistance training by improving cardiorespiratory fitness, muscular strength, and physical performance. Further research with larger cohort is necessary. CLINICAL TRIAL REGISTRATION NUMBER: ReBEC RBR-668c8v.

Muscle wasting after coronary artery bypass graft surgery: impact on post-operative clinical status and effect of exercise-based rehabilitation.

Background: Coronary artery bypass graft (CABG) surgery is known to induce significant muscle wasting. It remains to be investigated whether muscle wasting after CABG surgery relates to a worse clinical status at entry of rehabilitation and exercise-based rehabilitation remediates such muscle wasting.Design: Prospective observational study.Methods: In 21 males, changes in lean tissue mass (LTM) after CABG surgery were assessed and during a 12-week endurance exercise-based rehabilitation intervention. Changes in blood parameters and cardiopulmonary exercise capacity were assessed, and relations with changes in LTM were analysed.Results: LTM decreased by -1.9 ± 2.5 kg (p < .05) within 3 weeks after CABG surgery: greater LTM loss related to a lower ventilatory threshold at entry of rehabilitation (r = 0.58-0.61, p < .05). LTM was fully restored (+2.1 ± 2.4 kg, p < .05) during rehabilitation.Conclusion: In males, CABG-induced LTM reduction was associated with a worse aerobic exercise tolerance at entry of rehabilitation, but this LTM reduction was fully remediated by endurance exercise-based rehabilitation.

Impact of Exercise-Nutritional State Interactions in Patients with Type 2 Diabetes.

INTRODUCTION: This study examines the role of nutritional status during exercise training in patients with type 2 diabetes mellitus by investigating the effect of endurance-type exercise training in the fasted versus the fed state on clinical outcome measures, glycemic control, and skeletal muscle characteristics in male type 2 diabetes patients. METHODS: Twenty-five male patients (glycated hemoglobin (HbA1c), 57 ± 3 mmol·mol (7.4% ± 0.3%)) participated in a randomized 12-wk supervised endurance-type exercise intervention, with exercise being performed in an overnight-fasted state (n = 13) or after consuming breakfast (n = 12). Patients were evaluated for glycemic control, blood lipid profiles, body composition and physical fitness, and skeletal muscle gene expression. RESULTS: Exercise training was well tolerated without any incident of hypoglycemia. Exercise training significantly decreased whole-body fat mass (-1.6 kg) and increased high-density lipoprotein concentrations (+2 mg·dL), physical fitness (+1.7 mL·min·kg), and fat oxidation during exercise in both groups (PTIME < 0.05), with no between-group differences (PTIME × GROUP > 0.05). HbA1c concentrations significantly decreased after exercise training (PTIME < 0.001), with a significant greater reduction after consuming breakfast (-0.30% ± 0.06%) compared with fasted state (-0.08% ± 0.06%; mean difference, 0.21%; PTIME × GROUP = 0.016). No interaction effects were observed for skeletal muscle genes related to lipid metabolism or oxidative capacity. CONCLUSIONS: Endurance-type exercise training in the fasted or fed state do not differ in their efficacy to reduce fat mass, increase fat oxidation capacity, and increase cardiorespiratory fitness and high-density lipoprotein concentrations or their risk of hypoglycemia in male patients with type 2 diabetes. HbA1c seems to be improved more with exercise performed in the postprandial compared with the postabsorptive state.

A novel data fusion method for the effective analysis of multiple panels of flow cytometry data.

Multicolour flow cytometry (MFC) is used to measure multiple cellular markers at the single-cell level. Cellular markers may be coloured with different panels of fluorescently-labelled antibodies to enable cell identification or the detection of activated cells in pre-defined, 'gated' specific cell subsets. The number of markers that can be used per measurement is technologically limited however, requiring every panel to be analysed in a separate aliquot measurement. The combined analyses of these dedicated panels may enhance the predictive ability of these measurements and could enrich the interpretation of the immunological information. Here we introduce a fusion method for MFC data, based on DAMACY (Discriminant Analysis of Multi-Aspect Cytometry data), which can combine information from complementary panels. This approach leads to both enhanced predictions and clearer interpretations in comparison with the analysis of separate measurements. We illustrate this method using two datasets: the response of neutrophils evoked by a systemic endotoxin challenge and the activated immune status of the innate cells, T cells and B cells in obese versus lean individuals. The data fusion approach was able to detect cells that do not individually show a difference between clinical phenotypes but do play a role in combination with other cells.