Cardioprotective effect of intradialytic exercise on left atrial mechanics.

Left atrial (LA) function plays a pivotal role in cardiac performance by modulating left ventricular (LV) function. Impairments in LV function are commonly reported during hemodialysis (HD), but available data describing changes in LA function are limited. There is growing evidence of the cardioprotective effect of intradialytic exercise (IDE) on LV function, but studies analyzing its effect on LA function are scarce. Our aim was to evaluate whether IDE can limit the severity of HD-induced impairment in LA myocardial function. In this prospective, open-label, two-center randomized crossover trial, 56 stable individuals receiving HD participated in 2 HD sessions in random order: standard HD and a session incorporating 30 min of aerobic exercise. LA and LV global longitudinal strains (GLSs) were obtained before and at peak stress of HD (i.e., 30 min before the HD ending). IDE totally eradicated the decline in LA reservoir strain observed during HD (estimated difference: 3.1%, 95% confidence interval: 0.4/5.8, P = 0.02), whereas it did not affect the other components of LA mechanics. A similar result favoring IDE intervention was also demonstrated on GLS changes over the HD procedure (P < 0.001). Between-session differences of changes in GLS and LA reservoir strain were correlated (r = -0.32, P = 0.03). The cardioprotective effect of IDE disappeared in patients with LA enlargement (i.e., LA volume index >34 mL/m2). In conclusion, even a short duration of IDE at moderate intensity is effective in preventing HD-associated decline in LA reservoir function. Further research is needed to explore the long-term benefits of IDE on LA function.NEW & NOTEWORTHY A single bout of intradialytic exercise (IDE) at moderate intensity can prevent the hemodialysis-associated decline in left atrial (LA) function. This was partially explained by the relative preservation of left ventricular systolic function with IDE. Benefits of IDE on LA function were lost in patients with LA dilation. Further studies are needed to explore the mechanisms behind IDE-induced cardioprotection and evaluate the clinical impacts of the repetitive cardioprotective effects of IDE on LA function.

Major impact of vitamin D3 deficiency and supplementation on left ventricular torsional mechanics during dobutamine stress in uncomplicated type 2 diabetes.

BACKGROUND AND AIMS: Hypovitaminosis D is associated with the risk of diabetic complications. Its role in diabetic-related cardiac abnormalities remain poorly understood. We aimed therefore to evaluate the effect of vitamin D deficiency and supplementation on early left ventricular (LV) dysfunction in vitamin D deficient patients with uncomplicated T2D. METHODS AND RESULTS: Sixty-three consecutive T2D patients who had a diagnosis of vitamin D3 were prospectively recruited and allocated into 2 groups (25(OH)D < 20 ng/mL: VDD, >20 ng/mL VDND). Twenty-eight of them with 25(OH)D < 20 ng/mL benefited from a 3-month supplementation. At baseline and follow-up, after conventional echocardiography including evaluation of epicardial adipose tissue (EAT), both LV longitudinal (LS) and circumferential (CS) strains and rotation/twist mechanics were evaluated at rest and during dobutamine (DOB) stress. After treatment, T2D patients successfully normalized their 25(OH)D levels. The strongest associations between vitamin D deficiency and supplementation with LV myocardial function were noticed for torsional mechanics indexes under DOB. EAT correlated significantly (p < 0.01) with baseline 25(OH)D and was reduced after supplementation. Significant correlations were obtained between these 2 parameters with twist or apical rotation at baseline (p < 0.01) and between their delta changes at follow-up (p < 0.01) under DOB. Significant improvements in LS and CS (p < 0.05) under DOB were also underlined at follow-up, with major enhancements noticed in the apical region (p < 0.01) of the LV. CONCLUSIONS: This study provides the first evidences of the potential of vitamin D supplementation as an efficient prophylactic strategy to alleviate the progression of myocardial dysfunction in asymptomatic patients with uncomplicated T2D. CLINICALTRIALS: NCT03437421.

Cardioprotective Effect of Acute Intradialytic Exercise: A Comprehensive Speckle-Tracking Echocardiography Analysis.

SIGNIFICANCE STATEMENT: Hemodialysis (HD) can lead to acute left ventricular (LV) myocardial wall motion abnormalities (myocardial stunning) due to segmental hypoperfusion. Exercise during dialysis is associated with favorable effects on central hemodynamics and BP stability, factors considered in the etiology of HD-induced myocardial stunning. In a speckle-tracking echocardiography analysis, the authors explored effects of acute intradialytic exercise (IDE) on LV regional myocardial function in 60 patients undergoing HD. They found beneficial effects of IDE on LV longitudinal and circumferential function and on torsional mechanics, not accounted for by cardiac loading conditions or central hemodynamics. These findings support the implementation of IDE in people with ESKD, given that LV transient dysfunction imposed by repetitive HD may contribute to heart failure and increased risk of cardiac events in such patients. BACKGROUND: Hemodialysis (HD) induces left ventricular (LV) transient myocardial dysfunction. A complex interplay between linear deformations and torsional mechanics underlies LV myocardial performance. Although intradialytic exercise (IDE) induces favorable effects on central hemodynamics, its effect on myocardial mechanics has never been comprehensively documented. METHODS: To evaluate the effects of IDE on LV myocardial mechanics, assessed by speckle-tracking echocardiography, we conducted a prospective, open-label, two-center randomized crossover trial. We enrolled 60 individuals with ESKD receiving HD, who were assigned to participate in two sessions performed in a randomized order: standard HD and HD incorporating 30 minutes of aerobic exercise (HDEX). We measured global longitudinal strain (GLS) at baseline (T0), 90 minutes after HD onset (T1), and 30 minutes before ending HD (T2). At T0 and T2, we also measured circumferential strain and twist, calculated as the net difference between apical and basal rotations. Central hemodynamic data (BP, cardiac output) also were collected. RESULTS: The decline in GLS observed during the HD procedure was attenuated in the HDEX sessions (estimated difference, -1.16%; 95% confidence interval [95% CI], -0.31 to -2.02; P = 0.008). Compared with HD, HDEX also demonstrated greater improvements from T0 to T2 in twist, an important component of LV myocardial function (estimated difference, 2.48°; 95% CI, 0.30 to 4.65; P = 0.02). Differences in changes from T0 to T2 for cardiac loading and intradialytic hemodynamics did not account for the beneficial effects of IDE on LV myocardial mechanics kinetics. CONCLUSIONS: IDE applied acutely during HD improves regional myocardial mechanics and might warrant consideration in the therapeutic approach for patients on HD.

Cardiorespiratory Fitness and Bone Turnover Markers in Adults With Metabolic Syndrome: The Mediator Role of Inflammation.

The relationship between inflammatory markers and bone turnover in adults is well known, and a negative association between cardiorespiratory fitness (CRF) and inflammatory markers has also been described. Hence, we tested whether the association between CRF and bone turnover markers is mediated by inflammatory markers in adults with metabolic syndrome. A total of 81 adults (58.5 ± 5.0 years, 62.7% women) were included in the analysis. CRF was measured by the 6-min walking test. Serum interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor alpha, high-sensitivity c-reactive protein (hsCRP) and vascular endothelial growth factor, collagen type I cross-linked C-telopeptide, procollagen type I N-terminal propeptide (P1NP), and total osteocalcin were assessed using a sensitive ELISA kit. Body composition was assessed by dual-energy X-ray absorptiometry. Partial correlation was used to test the relationship between CRF, inflammatory markers, and bone turnover markers, controlling for sex, lean mass, and fat mass. Boot-strapped mediation procedures were performed, and indirect effects with confidence intervals not including zero were interpreted as statistically significant. CRF was positively correlated with P1NP levels (r = .228, p = .044) and osteocalcin levels (r = .296, p = .009). Furthermore, CRF was positively correlated with IL-1ß levels (r = .340, p = .002) and negatively correlated with hsCRP levels (r = -.335, p = .003), whereas IL-1ß levels were positively correlated with P1NP levels (r = .245, p = .030), and hsCRP levels were negatively correlated with P1NP levels (r = -.319, p = .004). Finally, the association between CRF and P1NP levels was totally mediated by hsCRP (percentage of mediation = 39.9). Therefore, CRF benefits on bone formation could be dependent on hsCRP concentrations in this population.

Additive effects of type 2 diabetes and metabolic syndrome on left ventricular torsion and linear deformation abnormalities during dobutamine stress echocardiography.

Objective: The interplay between metabolic syndrome (MS) and type 2 diabetes (T2D) on regional myocardial mechanics and the potential additional effects of their combination remain poorly understood. In this context, we evaluated left ventricular (LV) torsion and linear deformation at rest and under dobutamine (DB) stress in patients with T2D, MS or both. Methods: Thirty-nine T2D patients without MS (T2D), 37 MS patients free from T2D (MS), 44 patients with both T2D and MS (T2D-MS group) and 38 healthy patients (control group) were prospectively recruited. Speckle-tracking echocardiography (STE) was conducted at rest and low dose DB to evaluate LV myocardial longitudinal (LS) as well as circumferential (CS) strain and early diastolic strain rate (LSrd, CSrd) and twist-untwist mechanics. Results: At rest, MS, T2D and controls presented with similar resting LS and LSrd while significant lower values were obtained in T2D-MS compared to controls. DB revealed reduced LS, LSrd, CS and CSrd in MS and T2D groups compared to controls. In T2-MS, the decline in LS and LSrd established at rest was exacerbated under DB. Stress echocardiography revealed also lower basal rotation and subsequently lower twist in MS and T2D patients compared to controls. T2D-MS showed major impairments of apical rotation and twist under DB stress, with values significantly lower compared to the 3 other groups. From stepwise multiple linear regression analysis, epicardial adipose tissue for Δ (rest to DB) LS, numbers of MS factors for Δ CS and Δ Twist emerged as major independent predictors. Conclusion: These results demonstrate synergic and additive effects of T2D and MS on LV torsion and linear deformation abnormalities in asymptomatic patients with metabolic diseases. They also highlight the usefulness of speckle tracking echocardiography under DB stress in detecting multidirectional myocardial mechanics impairments that can remain barely detectable at rest, such as in isolated T2D or MS patients.

Corrigendum: Left Ventricular Strains and Myocardial Work in Adolescents With Anorexia Nervosa.

[This corrects the article DOI: 10.3389/fcvm.2022.798774.].

Cardiac Remodeling and Its Determinants in Anorexia Nervosa Adolescents: Impact of Weight Recovery.

Cardiovascular alterations in anorexia nervosa (AN) adolescents include bradycardia and decreased systolic blood pressure and left ventricular mass. However, their determinants remain poorly understood. We assessed the associations between morphological and functional left ventricular (LV) remodeling, autonomic control by heart rate variability (HRV) analysis, thyroid hormones and brain natriuretic peptide (BNP) levels in AN female adolescents without or with weight recovery (WR). Fifty-nine female adolescents including 16 AN patients without WR (mean age 13.9 years (10−16)), 10 AN patients with WR (15.7 years (12−18)) and 33 controls (14.1 years (10−18)) underwent night heart rate (HR) recording to measure HRV (and especially SD1/SD2, the ratio between instantaneous (SD1) and long-term (SD2) standard deviation of R-R intervals, reflecting sympatho-vagal balance), speckle tracking echocardiography to assess LV global longitudinal strain (GLS) and blood test for dosage of tri-iodothyronine (T3) hormone and NT-proBNP. Compared to controls, AN patients without WR presented with lower HR (55 ± 7 vs. 68 ± 6 bpm; p < 0.001), parasympathetic hyperactivity, and higher GLS (−19.2 ± 1.8 vs. −16.9 ± 2.8%; p = 0.009). These alterations were partly abolished in AN patients with WR. In a multivariate regression analysis, T3 was the main factor explaining the variance of SD1/SD2, a sympatho-vagal balance marker. NT-proBNP levels were not correlated with cardiac alterations. AN patients had parasympathetic hyperactivity linked with their rate of T3, and a higher GLS. These alterations were partly restored in AN patients with WR.

Non-invasive biomarkers of non-alcoholic fatty liver disease in patients with Metabolic Syndrome: insights from the RESOLVE study.

BACKGROUND: The aim of the present study was to evaluate i) the presence of liver steatosis using Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Liver Fat Score (LFS) in patients suffering from MS and ii) the association of FLI, HSI and LFS with the cardiometabolic risks. METHODS: A total of 91 patients with MS (MS; 39 men, 52 women) and 44 age matched healthy subjects (Control; 23 men and 21 women) were enrolled in the study. A continuous cardiometabolic score (MetsScore) and the noninvasive tests of hepatic steatosis were calculated for comparison and association analysis. RESULTS: Liver steatosis was detected in 86%, 84% and 80% of people diagnosed with MS using FLI, HSI and LFS respectively and MetsScore increases with FLI severity (p<0,05). Also, FLI and LFS were positively associated with MetsScore (p<0.01 and p<0.05 respectively) but not HSI. Multivariate linear regression models revealed that FLI has a stronger association with MetsScore compared with HSI and LFS (p<0,001). CONCLUSIONS: FLI is associated with the severity of MS and represent a good indicator to assess the relation between liver steatosis and a cardiometabolic disorders in clinical routine.

Anabolic Steroids Use Is Associated with Impairments in Atrial and Ventricular Cardiac Structure and Performance in Athletes.

PURPOSE: Despite potential severe cardiac side effects, anabolic androgenic steroids (AAS) are increasingly used by strength athletes. However, previous echocardiographic studies focused on the left ventricular (LV) strains but did not assess LV twist and untwist mechanics. Moreover, left atrial (LA) function has been often neglected, and its stiffness, an important determinant of LA reservoir function, has never been challenged. The aim of this study was to investigate the effects of AAS on LA and LV morphologies and functions in strength athletes. METHODS: Fifty subjects including 20 strength-trained young athletes age 32.0 ± 8.5 yr with a mean duration of AAS use of 4.7 ± 1.8 yr (users), 15 athletes with no history of AAS use (nonusers) and 15 sedentary controls underwent speckle tracking echocardiography to assess LA and LV morphology and function. RESULTS: Users showed higher LA reservoir dysfunction than nonusers (33.7% ± 10.9% vs 44.9% ± 9.9% respectively, P = 0.004) and higher LA stiffness (0.13 ± 0.05 vs 0.19 ± 0.08 A.U., respectively; P = 0.02), higher LV mass index and lower global and regional LV diastolic and systolic dysfunction (global longitudinal strain: -15.5% ± 3.2% vs -18.9% ± 1.8% respectively; P = 0.003), with a drop of LV twist-untwist mechanics (untwisting velocity: 61.5°·s-1 ± 20.2°·s-1 vs 73.7°·s-1 ± 16.1°·s-1 respectively, P = 0.04). There were significant correlations between LV mass and LV apical rotation (P = 0.003, r = 0.44) and diastolic longitudinal strain rate (P = 0.015, r = 0.33). CONCLUSIONS: Our results showing significant LA and LV remodeling and dysfunctions in young AAS using athletes are alarming. Screening echocardiography based on speckle tracking echocardiography parameters for early diagnosis, as well as a stronger awareness in athletes and in physicians are warranted in this context.

Vitamin D3 Supplementation Alleviates Left Ventricular Dysfunction in a Mouse Model of Diet-Induced Type 2 Diabetes: Potential Involvement of Cardiac Lipotoxicity Modulation.

PURPOSE: To evaluate the effectiveness of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function, as well as lipid profile, in a mouse model of diet-induced type 2 diabetes. METHODS: Mice were fed a high fat and sucrose diet for 10 weeks. Afterward, diet was maintained for 15 more weeks and two groups were formed, with and without cholecalciferol supplementation. A control group was fed with normal chow. Glucose homeostasis and cardiac function were assessed at baseline and at the 10th and 24th weeks. Animals were killed at the 10th and 25th weeks for plasma and cardiac sample analysis. Cardiac lipid profile was characterized by LC-MS/MS. RESULTS: After 10 weeks of diet, mice exhibited pre-diabetes, mild left ventricle hypertrophy, and impaired longitudinal strain, but preserved myocardial circumferential as well as global diastolic and systolic cardiac function. After 15 more weeks of diet, animals presented with well-established type 2 diabetes, pathological cardiac hypertrophy, and impaired regional myocardial function. Cholecalciferol supplementation had no effect on glucose homeostasis but improved cardiac remodeling and regional myocardial function. After 25 weeks, non-supplemented mice exhibited increased myocardial levels of ceramides and diacylglycerol, both of which were normalized by vitamin D3 supplementation. CONCLUSION: This work brought to light the beneficial effects of cholecalciferol supplementation, in secondary prevention, on cardiac remodeling and function in a mouse model of diet-induced type 2 diabetes. Those cardioprotective effects may be, at least in part, attributed to the modulation of myocardial levels of lipotoxic species by vitamin D.

Key role of left ventricular untwisting in endurance cyclists at onset of exercise.

The rise in oxygen consumption during the transition from rest to exercise is faster in those who are endurance-trained than those who have sedentary lifestyles, partly due to a more efficient cardiac response. However, data regarding this acute cardiac response in trained individuals are limited to heart rate (HR), stroke volume, and cardiac output. Considering this, we compared cardiac kinetics, including left ventricular (LV) strains and twist/untwist mechanics, between endurance-trained cyclists and their sedentary counterparts. Twenty young, male, trained cyclists and 23 untrained participants aged 18-25 yr performed five similar constant workload exercises on a cyclo-ergometer (target HR: 130 beats/min). During each session, LV myocardial diastolic and systolic linear strains, as well as torsional mechanics, were assessed using speckle-tracking echocardiography. Cardiac function was evaluated every 15 s during the first minute and every 30 s thereafter, until 240 s. Stroke volume increased during the first 30-45 s in both groups but to a significantly greater extent in trained cyclists (31% vs. 24%). Systolic parameters were similar in both groups. Transmitral peak filling velocity and peak filling rate responded faster to exercise and with greater amplitude in trained cyclists. Left ventricular filling pressure was lower in the former, whereas LV relaxation was greater but only at the base of the left ventricle. Basal rotation and peak untwisting rate responded faster and to a greater extent in the cyclists. This study provides new mechanical insights into the key role of LV untwisting in the more efficient acute cardiac response of endurance-trained athletes at onset of exercise.NEW & NOTEWORTHY Our study assessed for the first time, to our knowledge, the kinetics of left ventricular function during the transition from rest to constant-load exercise in endurance-trained subjects. We observed a faster cardiac response in cyclists characterized by a faster response of cardiac output, left ventricular transmitral filling, basal rotation, and untwisting. This study highlighted the key role of left ventricular twisting mechanics in the more efficient acute cardiac response of endurance-trained athletes at onset of exercise.

Left ventricular dyssynchrony and post-systolic shortening in young bodybuilders using anabolic-androgenic steroids.

Left ventricular (LV) remodeling, characterized by increased LV hypertrophy and depressed systolic and diastolic function, is observed in strength-trained athletes who use anabolic-androgenic steroids (AAS). Previous studies suggested a pathological remodeling with an increase in cardiac fibrosis in these athletes, which could promote intraventricular dyssynchrony. In this context, this study evaluated LV dyssynchrony in strength-trained athletes using AAS, hypothesizing that the use of AAS would lead to an increase in post-systolic shortening. Forty-four male subjects (aged 20-40 yr) were divided into three age-matched groups: strength-trained athletes using (users, n = 14) or not (nonusers, n = 15) AAS and healthy sedentary men (controls, n = 15). After completing a survey, each participant was assessed with two-dimensional (2D)-strain echocardiography. LV dyssynchrony was quantified using the standard deviation (SD) of the time to peak for longitudinal strain of the 18 LV-segments (from the apical 4, 3, and 2 chambers views), the longitudinal strain delay index (LSDI), and the segmental post-systolic index (PSI). Users showed mean AAS dosages of 564 ± 288 mg[Formula: see text]wk-1 with a mean protocol duration of 12 ± 6 wk and a history of use of 4.7 ± 1.8 yr. They exhibited a greater LV mass index and depressed systolic and diastolic function when compared with both nonusers and controls. The decrease in LV strain in users was predominantly observed at the interventricular septum level (-16.9% ± 2.5% vs. -19.2% ± 1.8% and -19.0% ± 1.6% in users, nonusers, and controls, respectively, P < 0.01). Users showed higher SD than controls (43 ± 8 ms vs. 32 ± 5 ms, respectively, P < 0.01). The LSDI was significantly higher in users compared with both nonusers and controls (-23.4 ± 9.5 vs. -15.9 ± 9.3 and -9.8 ± 3.9, respectively, P < 0.01). PSI, calculated on the basal inferoseptal, basal anteroseptal, and basal inferolateral segments, were also greater in users compared with the two other groups. Our results reported an increase in LV dyssynchrony in young AAS users that brought new evidences of a pathologic cardiac remodeling in this specific population.NEW & NOTEWORTHY Illicit androgenic anabolic steroids (AAS) use is widespread, but data on LV dyssynchrony are lacking, although it could be increased by a higher prevalence of myocardial fibrosis reported in this population. In AAS users, the decrease in LV strain was predominantly observed in interventricular segments. All dyssynchrony indices were higher in AAS users and several segments exhibited post-systolic shortening. These results showed an association between AAS consumption, LV remodeling, and dyssynchrony.

Combined Beneficial Effect of Voluntary Physical Exercise and Vitamin D Supplementation in Diet-induced Obese C57BL/6J Mice.

PURPOSE: Physical exercise (PE) combined with nutritional approaches has beneficial effects that are widely advocated to improve metabolic health. Here we used voluntary PE together with vitamin D (VD) supplementation, which has already shown beneficial effects in primary and tertiary prevention in obese mice models, to study their combined additive effects on body weight management, glucose homeostasis, metabolic inflammation, and liver steatosis as key markers of metabolic health. METHODS: Ten-week-old male C57BL/6J mice were fed a high-fat/sucrose (HFS) diet for 10 wk, then assigned to a 15-wk intervention period with PE, VD supplementation, or both PE and VD supplementation. Morphological, histological, and molecular phenotype data were characterized. RESULTS: The HFS-induced increases in body mass, adiposity, and adipocyte hypertrophy were improved by PE but not by VD supplementation. The HFS-induced inflammation (highlighted by chemokines mRNA levels) in inguinal adipose tissue was decreased by PE and/or VD supplementation. Furthermore, the intervention combining PE and VD showed additive effects on restoring insulin sensitivity and improving hepatic steatosis, as demonstrated through a normalization of size and number of hepatic lipid droplets and triglyceride content and a significant molecular-level decrease in the expression of genes coding for key enzymes in hepatic de novo lipogenesis. CONCLUSIONS: Taken together, our data show beneficial effects of combining PE and VD supplementation on obesity-associated comorbidities such as insulin resistance and hepatic disease in mice. This combined exercise-nutritional support strategy could prove valuable in obesity management programs.

Dietary Fibres and the Management of Obesity and Metabolic Syndrome: The RESOLVE Study.

OBJECTIVES: This study was performed to evaluate the long-term maintenance of nutritional changes promoted during an intensive initial intervention to induce body weight loss. The ability of these changes to predict long-term health outcomes was also examined. METHODS: Nutritional variables, body composition, and metabolic markers collected in the RESOLVE project were analyzed before and after a 3-week intensive diet-exercise intervention (Phase 1), and during a subsequent supervision under free living conditions, of 12 months (Phase 2). RESULTS: As expected, the macronutrient composition of the diet was modified to promote a negative energy balance during Phase 1. The decrease in carbohydrates imposed during this phase was maintained during Phase 2 whereas the increase in protein intake returned to baseline values at the end of the program. Dietary fiber intake was almost doubled during Phase 1 and remained significantly greater than baseline values throughout Phase 2. Moreover, fiber intake was the only nutritional variable that systematically and significantly predicted variations of health outcomes in the study. CONCLUSION: The adequacy of dietary fiber intake should be a matter of primary consideration in diet-based weight reduction programs.

Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice.

The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect of VD supplementation on obesity and associated disorders was evaluated in high-fat- and high-sucrose (HFS)-fed mice. Morphological, histological, and molecular phenotype were characterized. The increased body mass and adiposity caused by HFS diet as well as fat cell hypertrophy and glucose homeostasis were not improved by VD supplementation. However, VD supplementation led to a decrease of HFS-induced inflammation in inguinal adipose tissue, characterized by a decreased expression of chemokine mRNA levels. Moreover, a protective effect of VD on HFS-induced hepatic steatosis was highlighted by a decrease of lipid droplets and a reduction of triglyceride accumulation in the liver. This result was associated with a significant decrease of gene expression coding for key enzymes involved in hepatic de novo lipogenesis and fatty acid oxidation. Altogether, our results show that VD supplementation could be of interest to blunt the adipose tissue inflammation and hepatic steatosis and could represent an interesting nutritional strategy to fight obesity-associated comorbidities.

Stress management in obesity during a thermal spa residential programme (ObesiStress): protocol for a randomised controlled trial study.

INTRODUCTION: Stress and obesity are two public health issues. The relationship between obesity and stress is biological through the actions of stress on the major hormones that regulate appetite (leptin and ghrelin). Many spa resorts in France specialise in the treatment of obesity, but no thermal spa currently proposes a specific programme to manage stress in obesity. The ObesiStress protocol has been designed to offer a new residential stress management programme. This thermal spa treatment of obesity implements stress management strategies as suggested by international recommendations. METHODS AND ANALYSIS: 140 overweight or obese participants with a Body Mass Index of >25 kg/m2 and aged over 18 years will be recruited. Participants will be randomised into two groups: a control group of usual practice (restrictive diet, physical activity and thermal spa treatment) and an intervention group with stress management in addition to the usual practice. In the present protocol, parameters will be measured on five occasions (at inclusion, at the beginning of the spa (day 0), at the end of the spa (day 21), and at 6 and 12 months). The study will assess the participants' heart rate variability, cardiac remodelling and function, electrodermal activity, blood markers, anthropometric profile, body composition, psychology and quality of life via the use of questionnaires and bone parameters. ETHICS AND DISSEMINATION: The ObesiStress protocol complies with the ethics guidelines for Clinical Research and has been approved by the ethics committee (CPP Sud-Est VI, Clermont-Ferrand - ANSM: 2016-A01774-47). This study aimed to highlight the efficacy of a 21-day thermal spa residential programme of stress management in obesity through objective measurements of well-being and cardiovascular morbidity. Results will be disseminated during several research conferences and articles published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03578757.

Kinetics of Left Ventricular Mechanics during Transition from Rest to Exercise.

PURPOSE: At the onset of physical exercise, oxygen (O2) transport adapts to meet the working muscle O2 demands. Cardiac output abruptly increases through the concomitant changes of HR and stroke volume (SV), which is conditioned by the left ventricular (LV) function. The purpose of this study was to investigate the contribution of many LV diastolic and systolic function parameters, including twist-untwist mechanics, to SV adaptation during the first minutes after exercise onset. METHODS: Diastolic and systolic myocardial strains and twist were monitored by two-dimensional speckle-tracking echocardiography with high temporal resolution in 28 young men (mean age, 23 ± 4 yr) who performed five similar constant work-load exercises on a cycloergometer (target HR: 125 bpm). Two-dimensional cine-loops were recorded every 15 s during the first minute of exercise, and then every 30 s for the next 3 min. RESULTS: During the first 60 s of exercise, SV (from 104 ± 15 mL to 126 ± 21 mL, P < 0.001) increased concomitantly with LV strain and strain rates. Early filling was the main SV determinant during this phase, probably linked to the increase of venous return (at the very beginning of exercise), LV relaxation (from 1.5 ± 0.3 s to 2.5 ± 0.4 s, P < 0.001) and untwisting (from -78 ± 34°·s to -165 ± 61°·s, P < 0.001). After the first minute, SV remained constant, whereas LV untwisting continued to increase (from -165 ± 61°·s to -187 ± 60°·s, P < 0.001) and the other systolic and diastolic parameters reached a plateau. CONCLUSIONS: This study gives new mechanical insights into LV kinetics to address the challenge of SV response at the onset of exercise.

Long-term effects of high-intensity resistance and endurance exercise on plasma leptin and ghrelin in overweight individuals: the RESOLVE Study.

The objective of this study was to evaluate the effects of high-intensity resistance and endurance exercise on body composition and plasma leptin and ghrelin concentrations in overweight individuals. One hundred participants were randomly assigned to 3 exercise interventions: high-resistance-low-aerobic exercise (Re), low-resistance-high-aerobic exercise (rE), low-resistance-low-aerobic exercise (re). Interventions began with 3 weeks of residential supervision (phase 1) after which participants had to manage the physical activity programs individually (phase 2). Body composition and plasma variables were measured at baseline and after phase 1 as well as after 3, 6, and 12 months. Significant decreases in body weight and fat were observed after phase 1 (p < 0.001) and continued at a lower rate for up to 3 months and then remained stable for the rest of the protocol. Once a body weight plateau was reached, body fat loss after the Re and rE conditions exceeded the fat loss observed in the re condition by 1.5-2 kg (p < 0.05). Leptin was significantly decreased after day 21 and month 3 (p < 0.001) and remained stable for the rest of the study. Ghrelin was significantly increased after day 21 and month 3 (p < 0.001) and returned to a level comparable to baseline between month 6 and 12 when body weight and fat had reached a plateau. In conclusion, this study reinforces the idea that an increase in exercise intensity may accentuate body fat loss before the occurrence of a body weight plateau. Resistance to further fat loss was accompanied by a decrease in plasma leptin and an increase in plasma ghrelin.

Different modalities of exercise improve macrovascular function but not microvascular function in metabolic syndrome: The RESOLVE randomized trial.

OBJECTIVE: To determine which modality of exercise program (endurance and/or resistance dominance) is the most effective for improving vascular function in the micro- and macrocirculation in metabolic syndrome (MetS). METHODS: Sixty-two MetS patients were enrolled in a 6-month lifestyle intervention program based on diet and exercise training. Each participant was randomly assigned to one of 3 groups categorized by exercise modality (e.g. high-intensity resistance or endurance training, or combined moderate-intensity). Measurements of anthropometrics, biological blood markers, physical fitness and vascular function were performed at baseline, at the end of the 3-week residential program, and at 3 and 6 months after baseline. Brachial artery flow-mediated dilation (FMD) and the response to sublingual nitrate were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated using laser Doppler flowmetry in conjunction with iontophoresis of acetylcholine and sodium nitroprusside. RESULTS: Regardless of the training program, FMD significantly increased from baseline to 3 weeks in all groups with no further changes at 3 and 6 months. Changes in central fat, diastolic blood pressure, triglycerides, interleukin-6 and physical fitness were independent predictors of increased FMD. Nitrate-mediated dilation increased from baseline to 3 months and then remained unchanged up to 6 months. Endothelium-dependent and endothelium-independent function of the skin microcirculation did not change significantly in all groups. CONCLUSIONS: In MetS patients, exercise training, regardless of its endurance or resistance dominance, is able to improve vascular function in large vessels only. Lifestyle intervention programs including exercise training must be encouraged in those with MetS. NCT00917917.