Effects of an acute bout of exercise on circulating extracellular vesicles: tissue-, sex-, and BMI-related differences.

BACKGROUND: Exercise is recognized to evoke multisystemic adaptations that, particularly in obese subjects, reduce body weight, improve glucometabolic control, counteract sarcopenia, and lower the risk of cardiometabolic diseases. Understanding the molecular and cellular mechanisms of exercise-induced benefits is of great interest due to the therapeutic implications against obesity. OBJECTIVES AND METHODS: The aim of the present study was to evaluate time-related changes in size distribution and cell origin of extracellular vesicles (EVs) in obese and normal-weight subjects who underwent a moderate-intensity exercise on a treadmill (at 60% of their VO2max). Blood samples were drawn before, immediately at the end of the exercise and during the postexercise recovery period (3 and 24 h). Circulating EVs were analyzed by a nanoparticle tracking analysis and flow cytometry after labeling with the following cell-specific markers: CD14 (monocyte/macrophage), CD61 (platelet), CD62E (activated endothelium), CD105 (total endothelium), SCGA (skeletal muscle), and FABP (adipose tissue). RESULTS: In all subjects, acute exercise reduced the release of total (i.e., 30-700 nm) EVs in circulation, predominantly EVs in the microvesicle size range (i.e., 130-700 nm EVs). The postexercise release of microvesicles was higher in normal-weight than obese subjects; after exercise, circulating levels of exosomes (i.e., 30-130 nm EVs) and microvesicles were, respectively, lower and higher in females than males. In all experimental subgroups (males vs. females and obese vs. normal-weight subjects), acute exercise reduced and increased, respectively, CD61 + and SCGA + EVs, being the effect on CD61 + EVs prolonged up to 24 h after the end of the test with subjects in resting conditions. Total EVs, exosomes, and CD61 + EVs were associated with HOMA-IR. CONCLUSIONS: Though preliminary, the results of the present study show that a single bout of acute exercise modulates the release of EVs in circulation, which are tissue-, sex-, and BMI specific, suggesting that the exercise-related benefits might depend upon a complex interaction of tissue, endocrine, and metabolic factors.

Effects of a 3-Week In-Hospital Multidisciplinary Body Weight Reduction Program in Obese Females: Is Measured Resting Energy Expenditure Essential for Tailoring Adequately the Amount of Energy Intake?

In the obese population, the prescription of a proper diet plan is essential to ensure an appropriate and gradual weight loss, reduce the risk of weight cycling and favor an overall improvement of health conditions. Energy needs are commonly estimated using predictive equations, even if their accuracy is still debated, especially in severely obese subjects. In the present study, 850 severely obese females admitted to our hospital for a multidisciplinary body weight reduction program (BWRP) were divided into three subgroups, "hypo-," "normo-," and "hyper-metabolic," based on the comparison between estimated resting energy expenditure (eREE, using the Mifflin equation) and measured REE (mREE, using indirect calorimetry). The majority of this study population was considered normo-metabolic (59.4%, mREE between 90 and 110% of eREE), 32.6% was hyper-metabolic (mREE > 110% of eREE) and only 8% was hypo-metabolic (mREE < 90% of eREE). The three subgroups were evaluated before and after a 3-week BWRP, entailing energy restricted diet, adapted physical activity, psychological counseling and nutritional education. Since the diet plan during the BWRP consisted of a 30% reduction of total energy expenditure (obtained by multiplying mREE by the physical activity level), each subgroup responded positively to the BWRP independently from the difference between mREE and eREE, the extent of BMI reduction and clinical, metabolic and physical amelioration being comparable among the three subgroups. By contrast, the restriction of the energy intake based on eREE during the BWRP would have determined a slighter caloric restriction in the hypo-metabolic subgroup, thus determining a smaller body weight reduction, and, by contrast, a more marked caloric restriction in the hyper-metabolic subgroup, probably difficult to be tolerated and maintained for prolonged period. In conclusion, the percentage of subjects with "slow metabolism" in a Caucasian female obese population seeking hospitalization for a BWRP is actually lower than expected, finding controverting the common notion that obesity is mostly due to reduced REE. The high percentage (40%) of inadequate eREE in these female obese populations further underlines the absolute need to include the measurement of REE in the clinical practice for the correct prescription of energy intake in severely obese populations.

The Role of Different Indexes of Adiposity and Body Composition for the Identification of Metabolic Syndrome in Women with Obesity.

The aim of this study was to compare the accuracy of different indexes of adiposity and/or body composition in identifying the metabolic syndrome (MetS) in a group of 1528 Caucasian women with obesity: (age ± standard deviation (SD): 50.8 ± 14 years (range 18-83); body mass index (BMI) 43.3 ± 5.9 kg/m2 (30.7-72.9 kg/m2)). The following indexes were assessed in each subject: BMI, fat-free mass index (FFMI), fat mass index (FMI), tri-ponderal mass index (TMI), waist-to-height ratio (WtHR), and the body mass fat index (BMFI). Thereafter, a threshold value adjusted for age, which could identify MetS, was calculated for each index. A significant correlation was found among all indexes (p < 0.0001 for all). However, when the area under the curve (AUC) was compared, WtHR performed significantly better in the whole group and in the different age groups, apart from a lack of statistical difference between WtHR and BMFI in the 45-55 years age group. In conclusion, WtHR seems to be a fair index useful for identifying MetS in women with obesity. The use of thresholds appropriate for age can help further improve its accuracy, thus reinforcing the clinical evaluation for MetS screening.

Association of Serum Bilirubin Level with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study of 1672 Obese Children.

As in adults, obesity also plays a central role in the development of metabolic syndrome (MS) in children. Non-alcoholic fatty liver disease (NAFLD) is considered a manifestation of MS. Not only MS but also NAFLD seem to be inversely associated with serum bilirubin concentrations, an important endogenous tissue protector when only mild elevated. The aim of the study was to evaluate the association between serum bilirubin levels and the prevalence of MS and NAFLD in Italian obese children and adolescents. A retrospective cross-sectional study was performed in 1672 patients aged from 5 to 18 years. Clinical and laboratory parameters were assessed. NAFLD was measured by liver ultrasonography. The study was approved by the Ethical Committee of the Istituto Auxologico Italiano (research project code 1C021_2020, acronym BILOB). MS was present in 24% and fatty liver (FL) in 38% of this population. Bilirubin was not associated with FL and MS as a whole, but it was inversely associated only with selected components of MS, i.e., large WC, high blood pressure and high triglycerides. Our data suggest that bilirubin is not protective against MS and NAFLD in the presence of severe obesity.

Development and Internal Validation of Fatty Liver Prediction Models in Obese Children and Adolescents.

To develop predictive models of fatty liver (FL), we performed a cross-sectional retrospective study of 1672 obese children with a median (interquartile range) age of 15 (13-16) years. The outcome variable was FL diagnosed by ultrasonography. The potential predictors were: (1) binary: sex; (2) continuous: age, body mass index (BMI), waist circumference (WC), alanine transaminase (ALT), aspartate transaminase, gamma-glutamyltransferase, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), HDL-cholesterol, LDL-cholesterol, triglycerides, mean arterial pressure, uric acid, and c-reactive protein; (3) ordinal: Pubertal status. Bootstrapped multivariable logistic regression with fractional polynomials was used to develop the models. Two models were developed and internally validated, one using BMI and the other using WC as the anthropometric predictor. Both models included ALT, HOMA-IR, triglycerides, and uric acid as predictors, had similar discrimination (c-statistic = 0.81), and were similarly well calibrated as determined by calibration plots. These models should undergo external validation before being employed in clinical or research practice.

The Age-Dependent Increase of Metabolic Syndrome Requires More Extensive and Aggressive Non-Pharmacological and Pharmacological Interventions: A Cross-Sectional Study in an Italian Cohort of Obese Women.

BACKGROUND: Metabolic syndrome is a combination of cardiovascular risk factors (i.e., visceral obesity, dyslipidaemia, glucose intolerance, and hypertension), which entails critical issues in terms of medical management and public health. METHODS: The aim of the present cross-sectional study was to investigate the age-related changes of the single IDF (International Diabetes Federation) diagnostic criteria for metabolic syndrome (waist circumference, WC; high-density lipoprotein cholesterol, HDL-C; triglycerides; glucose; systolic and diastolic blood pressure, SBP and DBP) in a large population of (Italian) obese women (n = 1.000; body mass index, BMI >30 kg/m2; age: 18-83 yrs), subdivided into two subgroups depending on the presence (n = 630) or absence (n = 370) of metabolic syndrome. Parallelly, the percentages of treatment with hypolipidaemic drugs, hypoglycaemics, and antihypertensives and, among the treated subjects, of control of the underlying condition in accordance with the cut-offs of IDF criteria for dyslipidaemia, hyperglycaemia, and hypertension were determined over six age ranges (i.e., 18-30, 31-40, 41-50, 51-60, 61-70, and > 70 yrs). RESULTS: The prevalence of metabolic syndrome increased with advancing age. In the subgroup with metabolic syndrome, an age-dependent increase in HDL-C, glycaemia, and SBP occurred, while the visceral adiposity was stable. In the same subgroup, triglycerides and DBP decreased age-dependently. In the subgroup without metabolic syndrome, an age-dependent increase in WC, HDL-C, glycaemia, SBP, and DBP was observed. A progressive age-dependent increase in the percentage of patients pharmacologically treated for the cardiometabolic abnormalities was detected in patients with metabolic syndrome, a similar trend being also observed in patients without metabolic syndrome only for the antihypertensives. A clear-cut disproportion between treated versus adequately controlled women (with pharmacotherapy) was detected in the whole population. CONCLUSIONS: At least in an Italian context of obese females, the age-dependent worsening of glycaemia and BP exerts a fundamental pathophysiological role in the progressive increase of metabolic syndrome with advancing age, which appears to be not adequately treated in a large part of obese subjects. The results of the present study might be useful for public health decision-makers for programming future more extensive and aggressive non-pharmacological and pharmacological interventions in the obese population.

Use of a Pediatric Obesity Fall-risk Scale (POFS) in 301 hospitalized obese children and adolescents.

PURPOSE: Falls are a significant safety risk in hospitalized patients, but little evidence regarding their significance in obese children are available to date. Aim of the study was to determine whether the Pediatric Obesity Fall-risk Scale (POFS) is able to discriminate between hospitalized obese pediatric patients at high or low risk of falling, to evaluate its sensitivity and specificity and to analyze if the risk factors considered were actually related to the falling event. DESIGN AND METHODS: The sample consisted of 301 children and adolescents hospitalized for a body weight reduction program. In this 12-month study, 14.6% of patients experienced a fall during hospitalization, the fall rate per 1000 patient days being 5.33 for the first and 4.36 for the second 6-month of the year. The components of the POFS included chronological age, history of falls, body mass index standard deviation score (BMI-SDS), and the ability to maintain equilibrium. RESULTS: No differences were observed between fallers and nonfallers as far as BMI and BMI-SDS are concerned. Compared with patients who did not fall, those who fell were significantly younger and shorter and their weights were lower. The POFS identified 85 patients with high and 216 with low falling risk, the two subgroups being comparable for BMI and BMI-SDS. Compared with patients with low fall-risk, those with high fall-risk were significantly younger and shorter and their weights were lower. The sensitivity of the POFS was 61.4%, while the specificity was 77.4%. The positive predictive value of the POFS was 31.8%, while the negative predictive value was 92.1%. The analyses of each POFS component did not show significant differences between fallers and non-fallers in terms of BMI-SDS and equilibrium test. Compared with patients who did not fall, those who fell were significantly younger, experienced a fall during the 3 months prior the admission in hospital and their total POFS score was higher. PRACTICE IMPLICATIONS: Preventing falls in hospitalized obese pediatric patients is challenging due to the markedly increased risk of this population and specific fall-risk assessment tools are required to early identify patients who needs more care, attention, and specific nursing/medical interventions.

Changes of Body Weight and Body Composition in Obese Patients with Prader-Willi Syndrome at 3 and 6 Years of Follow-Up: A Retrospective Cohort Study.

Few short-term studies of weight loss have been performed in adult patients with Prader-Willi syndrome (PWS) undergoing metabolic rehabilitation. We performed a retrospective cohort study of 45 adult obese PWS patients undergoing a long-term multidisciplinary metabolic rehabilitation program based on diet and physical activity. Body composition was evaluated by dual-energy X-ray absorptiometry in 36 (80%) patients. The mean (95% CI) weight change was -3.6 (-7.6 to 0.4, p = 0.08) kg at 3 years and -4.6 (-8.5 to -0.8, p = 0.02) kg at 6 years, and that of BMI was -1.7 (-3.4 to 0.1, p = 0.06) kg/m2 at 3 years and -2.1 (-3.8 to -0.4, p = 0.02) kg/m2 at 6 years. A decrease of about 2% in fat mass per unit of body mass was observed, which is in line with the expectations for moderate weight loss. A possibly clinically relevant decrease in total and low-density lipoprotein cholesterol was also observed. These long-term results are important for patients with PWS, which is characterized by severe hyperphagia, behavioral disturbances, and cognitive impairment and is generally considered "resistant" to classical weight loss interventions.

The Appetite-Suppressant and GLP-1-Stimulating Effects of Whey Proteins in Obese Subjects are Associated with Increased Circulating Levels of Specific Amino Acids.

The satiating effect of whey proteins depends upon their unique amino acid composition because there is no difference when comparing whey proteins or a mix of amino acids mimicking the amino acid composition of whey proteins. The specific amino acids underlying the satiating effect of whey proteins have not been investigated to date. AIMS AND METHODS: The aim of the present study was to evaluate the appetite-suppressant effect of an isocaloric drink containing whey proteins or maltodextrins on appetite (satiety/hunger measured by a visual analogue scale or VAS), anorexigenic gastrointestinal peptides (circulating levels of glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY)) and amino acids (circulating levels of single, total [TAA] and branched-chain amino acids [BCAA]) in a cohort of obese female subjects (n = 8; age: 18.4 ± 3.1 years; body mass index, BMI: 39.2 ± 4.6 kg/m2). RESULTS: Each drink significantly increased satiety and decreased hunger, the effects being more evident with whey proteins than maltodextrins. Similarly, circulating levels of GLP-1, PYY and amino acids (TAA, BCAA and alanine, arginine, asparagine, citrulline, glutamine, hydroxyproline, isoleucine, histidine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tyrosine, and valine) were significantly higher with whey proteins than maltodextrins. In subjects administered whey proteins (but not maltodextrins), isoleucine, leucine, lysine, methionine, phenylalanine, proline, tyrosine, and valine were significantly correlated with hunger (negatively), satiety, and GLP-1 (positively). CONCLUSIONS: Eight specific amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, proline, tyrosine, and valine) were implicated in the appetite-suppressant and GLP-1-stimulating effects of whey proteins, which may be mediated by their binding with nutrient-sensing receptors expressed by L cells within the gastrointestinal wall. The long-term satiating effect of whey proteins and the effectiveness of a supplementation with these amino acids (i.e., as a nutraceutical intervention) administered during body weight reduction programs need to be further investigated.

Effects of a 3-Week In-Hospital Body Weight Reduction Program on Cardiovascular Risk Factors, Muscle Performance, and Fatigue: A Retrospective Study in a Population of Obese Adults with or without Metabolic Syndrome.

BACKGROUND: In clinical practice, there is the diffuse conviction that obese subjects with metabolic syndrome may be more difficult to treat. OBJECTIVES AND METHODS: The aim of the present study was that to investigate the effectiveness of a 3-week in-hospital body weight reduction program (BWRP) in a large population of obese subjects with and without metabolic syndrome (n = 1922; 222 men and 1700 women, age range 18-83 yr). Outcomes such as body mass index (BMI), total (TOT) and HDL cholesterol, systolic and diastolic blood pressures (SBP and DBP, respectively), coronary heart disease (CHD) score, fatigue severity score (FSS), and stair climbing test (SCT) time were evaluated before and after the intervention (Δ). A sex-, BMI-, and age-related stratification of the obese population with or without metabolic syndrome was applied. RESULTS: When compared to obese subjects without metabolic syndrome, at the basal conditions, obese subjects had a poorer cardiometabolic profile, as demonstrated by higher triglycerides, TOT-cholesterol, DBP, SBP, and CHD score, and a more compromised muscle performance (evaluated by SCT), associated with more perception of fatigue (measured by FSS). Nevertheless, obese subjects with metabolic syndrome obtained more benefits from BWRP than those without metabolic syndrome for some outcomes (i.e., ΔTOT-cholesterol, ΔSBP, and ΔCHD score). Despite these differences, the BWRP-induced weight loss was similar between the two groups (i.e., ΔBMI) as well as the gain of muscle performance (i.e., ΔSCT) and the reduction of fatigue (i.e., ΔFSS). Interestingly, the potentially deleterious fall in HDL-cholesterol levels after BWRP was less evident in obese subjects with metabolic syndrome than those without metabolic syndrome. When pooling all data, the ΔCHD score was associated with age, sex, and metabolic syndrome. The remaining outcomes, such as ΔBMI, ΔFSS, and ΔSCT time, were associated with sex and age but not with metabolic syndrome. Finally, ΔBMI was positively correlated with ΔCHD score, ΔFSS, and ΔSCT time in both obese subjects without metabolic syndrome and obese subjects with metabolic syndrome. CONCLUSIONS: When comparing obese subjects undergoing a BWRP, metabolic syndrome is not a negative predictive factor affecting the effectiveness of this intervention in terms of weight loss, muscle performance, and psychological well-being.

Evaluation of an Amino Acid Mix on the Secretion of Gastrointestinal Peptides, Glucometabolic Homeostasis, and Appetite in Obese Adolescents Administered with a Fixed-Dose or ad Libitum Meal.

Proteins have been demonstrated to reduce food intake in animals and humans via peripheral and central mechanisms. Supplementation of a dietetic regimen with single or mixed amino acids might represent an approach to improve the effectiveness of any body weight reduction program in obese subjects. The aim of the present study was to evaluate the effects of an amino acid mix (L-arginine + L-leucine + L-glutamine + L-tryptophan) on the secretion of some gastrointestinal peptides (i.e., ghrelin and glucagon-like peptide type 1, GLP-1), glucometabolic homeostasis (i.e., glucose, insulin, and glucagon), and appetite (hunger/satiety scored by visual analogue scale, VAS) in obese adolescents (n = 14; 10 females and 4 males; age: 16.6 ± 1.0 years; body mass index (BMI): 36.4 ± 4.6 kg/m²; fat-free mass (FFM): 54.9 ± 4.7%; fat mass (FM): 45.1 ± 4.4%) administered with a fixed-dose (lunch) or ad libitum (dinner) meal. Isocaloric maltodextrins were used as control treatment. During the lunch test, a significant increase in circulating levels of GLP-1, but not of ghrelin, was observed in the amino acid-treated group, which was congruent with significant changes in appetite, i.e., increase in satiety and decrease in hunger. A significant hyperglycemia was found in the maltodextrin-treated group during the prelunch period, without any significant changes in insulin and glucagon between the two groups. During the dinner test, there were no significant differences in appetite (hunger/satiety) and intake of calories. In conclusion, L-arginine, L-leucine, L-glutamine, and L-tryptophan, when administered to obese adolescents with a fixed-dose meal, are capable of evoking an anorexigenic response, which is, at least in part, mediated by an increase in GLP-1 released in circulation by L cells, which are capable of chemosensing specific amino acids present in the intestinal lumen. Further additional studies are requested to understand whether higher doses are necessary to inhibit ad libitum feeding.

Multidisciplinary Integrated Metabolic Rehabilitation in Elderly Obese Patients: Effects on Cardiovascular Risk Factors, Fatigue and Muscle Performance.

BACKGROUND: Obesity is a widespread problem in the elderly, being associated with severe comorbidities negatively influencing life expectancy. Integrated multidisciplinary metabolic rehabilitation aimed to reduce body weight (BW) and fatigue, increase physical autonomy and introduce healthy life style changes has been proposed as a useful intervention to improve the general health status and quality of life of the obese geriatric population. METHODS: Six hundred-eighty four severely obese subjects (F/M = 592/92; age range: 61-83 years; mean body mass index, BMI ± SD: 42.6 ± 5.6 kg/m2) were admitted to take part in a three-week in-hospital BW reduction program (BWRP), entailing energy restricted diet, psychological counselling, physical rehabilitation and nutritional education. Biochemical parameters, cardiovascular risk factors (throughout the Coronary Heart Disease Risk, CHD-R), fatigue (throughout the Fatigue Severity Scale, FSS) and lower limb muscle performance (throughout the Stair Climbing Test, SCT) were evaluated before and at the end of the BWRP. RESULTS: A 4% BW reduction was achieved at the end of the BWRP. This finding was associated with a significant improvement of the metabolic homeostasis (i.e., decrease in total cholesterol and glucose) and a reduction of systolic blood pressure in both females and males, thus resulting in a reduction of CHD-R in the male group. Total FSS score and SCT time decreased in female and male obese patients. The effects of BWPR were comparable among all age-related subgroups (>60, 60-69 and >70 years), apart from ΔCHD-R, which was higher in male subgroups. Finally, age was negatively correlated with ΔBMI and ΔFSS. CONCLUSIONS: Though only a relatively limited number of outcomes were investigated, the present study shows that a 4% BW reduction in severely elderly obese patients is associated with positive multisystemic effects, particularly, muscle-skeletal and cardiometabolic benefits, which can favorably influence their general well-being and improve the autonomy level in performing more common daily activities. The maintenance of a healthy life style, including controlled food intake and regular physical activity, after a BWRP is obviously recommended in all elderly obese patients to further improve their clinical condition.

Whey Proteins Reduce Appetite, Stimulate Anorexigenic Gastrointestinal Peptides and Improve Glucometabolic Homeostasis in Young Obese Women.

INTRODUCTION: Proteins, particularly whey proteins, represent the most satiating macronutrient in animals and humans. A dietetic regimen based on proteins enriched preload before eating might be a strategy to counteract obesity. AIMS AND METHODS: The aim of the present study was to evaluate the effects of an isocaloric drink containing whey proteins or maltodextrins (preload) on appetite (satiety/hunger measured by a visual analogue scale or VAS), glucometabolic control (blood glucose/insulin), and anorexigenic gastrointestinal peptides (pancreatic polypeptide or PP, glucagon-like peptide 1 or GLP-1 and peptide YY or PYY) in a cohort of obese young women (n = 9; age: 18.1 ± 3.0 years; body mass index, BMI: 38.8 ± 4.5 kg/m²). After two and a half hours, they were administered with a mixed meal at a fixed dose; satiety and hunger were measured by VAS. RESULTS: Each drink significantly augmented satiety and reduced hunger, and the effects were more evident with whey proteins than maltodextrins. Similarly, there were significant increases in GLP-1 and PYY levels (but not PP) after the ingestion of each drink; these anorexigenic responses were higher with whey proteins than maltodextrins. While insulinemia identically increased after each drink, whey proteins induced a lower glycemic response than maltodextrins. No differences in satiety and hunger were found after the meal, which is presumably due to the late administration of the meal test, when the hypophagic effect of whey proteins was disappearing. CONCLUSIONS: While whey proteins actually reduce appetite, stimulate anorexigenic gastrointestinal peptides, and improve glucometabolic homeostasis in young obese women, further additional studies are mandatory to demonstrate their hypophagic effects in obese subjects, when administered as preload before eating.