Identification of a Specific Plasma Sphingolipid Profile in a Group of Normal-Weight and Obese Subjects: A Novel Approach for a "Biochemical" Diagnosis of Metabolic Syndrome?

Metabolic syndrome is nosographically defined by using clinical diagnostic criteria such as those of the International Diabetes Federation (IDF) ones, including visceral adiposity, blood hypertension, insulin resistance and dyslipidemia. Due to the pathophysiological implications of the cardiometabolic risk of the obese subject, sphingolipids, measured in the plasma, might be used to biochemically support the diagnosis of metabolic syndrome. A total of 84 participants, including normal-weight (NW) and obese subjects without (OB-SIMET-) and with (OB-SIMET+) metabolic syndrome, were included in the study, and sphingolipidomics, including ceramides (Cer), dihydroceramides (DHCer), hexosyl-ceramides (HexCer), lactosyl-ceramides (LacCer), sphingomyelins (SM) and GM3 ganglosides families, and sphingosine-1-phosphate (S1P) and its congeners, was performed in plasma. Only total DHCers and S1P were significantly higher in OB-SIMET+ than NW subjects (p < 0.05), while total Cers decreased in both obese groups, though statistical significance was reached only in OB-SIMET- (vs. NW) subjects (p < 0.05). When considering the comparisons of the single sphingolipid species in the obese groups (OB-SIMET- or OB-SIMET+) vs. NW subjects, Cer 24:0 was significantly decreased (p < 0.05), while Cer 24:1, DHCer 16:0, 18:0, 18:1 and 24:1, and SM 18:0, 18:1 and 24:1 were significantly increased (p < 0.05). Furthermore, taking into account the same groups for comparison, HexCer 22:0 and 24:0, and GM3 22:0 and 24:0 were significantly decreased (p < 0.05), while HexCer 24:1 and S1P were significantly increased (p < 0.05). After having analyzed all data via a PLS-DA-based approach, the subsequent determination of the VIP scores evidenced the existence of a specific cluster of 15 sphingolipids endowed with a high discriminating performance (i.e., VIP score > 1.0) among the three groups, including DHCer 18:0, DHCer 24:1, Cer 18:0, HexCer 22:0, GM3 24:0, Cer C24:1, SM 18:1, SM 18:0, DHCer 18:1, HexCer 24:0, SM 24:1, S1P, SM 16:0, HexCer 24:1 and LacCer 22:0. After having run a series of multiple linear regressions, modeled by inserting each sphingolipid having a VIP score > 1.0 as a dependent variable, and waist circumference (WC), systolic/diastolic blood pressures (SBP/DBP), homeostasis model assessment-estimated insulin resistance (HOMA-IR), high-density lipoprotein (HDL), triglycerides (TG) (surrogates of IDF criteria) and C-reactive protein (CRP) (a marker of inflammation) as independent variables, WC was significantly associated with DHCer 18:0, DHCer 24:1, Cer 18:0, HexCer 22:0, Cer 24:1, SM 18:1, and LacCer 22:0 (p < 0.05); SBP with Cer 18:0, Cer 24:1, and SM 18:0 (p < 0.05); HOMA-IR with DHCer 18:0, DHCer 24:1, Cer 18:0, Cer 24:1, SM 18:1, and SM 18:0 (p < 0.05); HDL with HexCer 22:0, and HexCer 24:0 (p < 0.05); TG with DHCer 18:1, DHCer 24:1, SM 18:1, and SM 16:0 (p < 0.05); CRP with DHCer 18:1, and SP1 (p < 0.05). In conclusion, a cluster of 15 sphingolipid species is able to discriminate, with high performance, NW, OB-SIMET- and OB-SIMET+ groups. Although (surrogates of) the IDF diagnostic criteria seem to predict only partially, but congruently, the observed sphingolipid signature, sphingolipidomics might represent a promising "biochemical" support for the clinical diagnosis of metabolic syndrome.

Pediatric quality of life multidimensional fatigue scale (PedsQL-MFS) detects the effects of a 3-week Inpatient body weight reduction program for children and adolescents with obesity.

BACKGROUND: Fatigue is a frequent complaint amongst children and adolescents with obesity, and it interferes with adherence to dietary and exercise regimes that could reduce obesity. The present study evaluated the effect of an inpatient 3-week body weight reduction program on body weight and fatigue. METHOD: One hundred children and adolescents with obesity (64% female; aged 11-18 years) undertook an inpatient program of personalized diet, daily exercise, education, and counselling. RESULTS: The sample evidenced a mean reduction in body mass (females: ΔM = 4.3 (sd = 2.1) kg, p < .001), males: ΔM = 6.2 (sd = 2.6) kg, p < .001), BMI standard deviation score (females: ΔM = 0.17 (sd = 0.07), males: ΔM = 0.24 (sd = 0.08), p < .001) and fatigue (females: ΔM = 7.8 (sd = 9.7), males: ΔM = 5.0 (sd = 6.9), p < .001) as measured by the Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS) and improvements on the Attention problems subscale of the Youth Self Report (total sample: ΔM = 0.89 (sd = 2.44), p < .001). Reliable change analyses revealed fatigue changes were achieved by up to 34% females and 17% males, but the majority did not achieve reliable change and changes in fatigue were not correlated with changes in body mass. CONCLUSIONS: The program achieved clinically significant improvements in some children and adolescents. Future studies should explore predictors of treatment responsiveness. Trial registration Observational study. Not registered.

Factor structure, reliability, inter-rater agreement and convergent validity of the parent and child Italian versions of the paediatric quality of life inventory multidimensional fatigue scale for children and adolescents in paediatric inpatients with obesity and their parents.

OBJECTIVE: This study aimed to examine the factor structure, reliability, inter-rater agreement and convergent validity of the child and parent Italian versions of the paediatric quality of life inventory multidimensional fatigue scale (PedsQL-MFS) in paediatric inpatients with obesity and one of their parents. METHODS: 100 pairs of children/adolescents (64% female, mean age = 15.34) with obesity and one of their parents completed the PedsQL-MFS and the Child Behaviour Checklist (CBCL) or the Youth Self Report. RESULTS: Confirmatory Factor Analysis indicated that the three correlated first-order factors model corresponding to the published subscales demonstrated acceptable fit and achieved strict invariance across parent and child informants. Bifactor Analysis supported the multidimensionality and the reliability of the total and subscale scores as multidimensional composites. Parent-child agreement was low with latent means higher for parent reports. PedsQL-MFS total scores were strongly correlated with Somatic Complaints scores on the CBCL, and moderately associated with anxiety, depression, social problems and school problems. CONCLUSIONS: Total scores of the child and parent Italian versions of the PedsQL-MFS demonstrated good reliability and convergent validity in paediatric inpatients with obesity and their parents, and are complementary rather than interchangeable. LEVEL OF EVIDENCE: No level of evidence.

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.

Obesity-associated poor muscle quality: prevalence and association with age, sex, and body mass index.

BACKGROUND: Muscle quality (i.e., the expression of muscle function per unit of muscle mass) has been proposed as a clinically-relevant measure to detect individuals at risk of functional incapacity. Individuals with obesity might be at an increased risk of having poor muscle quality. Thus, we aimed to analyze the prevalence of poor muscle quality in obese individuals, to determine associated variables, and to provide normative values for this population. METHODS: 203 individuals with obesity (103 women, age: 18-75 years, body mass index (BMI): 35-64 kg·m- 2) participated in this cross-sectional study. Their muscle strength (handgrip dynamometry), muscle power (sit-to-stand test) and muscle mass (bioelectrical impedance analysis) were measured, and muscle quality (strength/power to muscle mass ratio) was compared with reference values obtained in young healthy individuals. Muscle quality was individually categorized as normal, low or poor based on specific muscle strength and power (i.e., strength and power per unit of muscle mass, respectively). Sex and age-specific normative values of specific muscle strength and power were computed for the whole cohort. RESULTS: Age and being a woman were inversely associated with specific muscle strength, with age being also inversely associated with specific muscle power. A small proportion of participants (6%) presented with an impaired (i.e., low/poor) specific muscle power while most of them (96%) had impaired specific muscle strength. Eventually, 84% of the participants were deemed to have poor muscle quality. Being a woman (odds ratio [OR]: 18.09, 95% confidence intervals [CI]: 4.07-80.38), age (OR: 1.06, 95%CI: 1.03-1.10) and BMI (OR: 1.22, 95%CI: 1.07-1.38) were independently associated with a higher risk of poor muscle quality in adjusted analyses. CONCLUSIONS: These findings show a high prevalence of poor muscle quality among individuals with obesity, with age, sex and BMI being independent predictors.

Ergogenic effects of beetroot juice supplementation during severe-intensity exercise in obese adolescents.

Previous studies showed a higher O2 cost of exercise, and therefore, a reduced exercise tolerance in patients with obesity during constant work rate (CWR) exercise compared with healthy subjects. Among the ergogenic effects of dietary nitrate ([Formula: see text]) supplementation in sedentary healthy subjects, a reduced O2 cost and enhanced exercise tolerance have often been demonstrated. The aim of this study was to evaluate the effects of beetroot juice (BR) supplementation, rich in [Formula: see text], on physiological variables associated with exercise tolerance in adolescents with obesity. In a double-blind, randomized crossover study, 10 adolescents with obesity (8 girls, 2 boys; age = 16 ± 1 yr; body mass index = 35.2 ± 5.0 kg/m2) were tested after 6 days of supplementation with BR (5 mmol [Formula: see text] per day) or placebo (PLA). Following each supplementation period, patients carried out two repetitions of 6-min moderate-intensity CWR exercise and one severe-intensity CWR exercise until exhaustion. Plasma [Formula: see text] concentration was significantly higher in BR versus PLA (108 ± 37 vs. 15 ± 5 µM, P < 0.0001). The O2 cost of moderate-intensity exercise was not different in BR versus PLA (13.3 ± 1.7 vs. 12.9 ± 1.1 ml·min-1·W-1, P = 0.517). During severe-intensity exercise, signs of a reduced amplitude of the O2 uptake slow component were observed in BR, in association with a significantly longer time to exhaustion (561 ± 198 s in BR vs. 457 ± 101 s in PLA, P = 0.0143). In obese adolescents, short-term dietary [Formula: see text] supplementation is effective in improving exercise tolerance during severe-intensity exercise. This may prove to be useful in counteracting early fatigue and reduced physical activity in this at-risk population.

Relationship between glucose metabolism and non-alcoholic fatty liver disease severity in morbidly obese women.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of type 2 diabetes mellitus (T2DM). Insulin resistance and beta-cell dysfunction are involved in the pathogenesis of T2DM. Insulin resistance is associated with NAFLD but little is known about beta-cell dysfunction and NAFLD. AIM: We tested whether NAFLD severity is associated with insulin sensitivity and beta-cell function in morbidly obese women. SUBJECTS AND METHODS: We studied 61 Caucasian women aged 18-60 years without T2DM and with a body mass index ranging from 35.3 to 48.8 kg/m². The insulin sensitivity index (ISI) and the disposition index (DI) from oral glucose tolerance testing were used as measures of insulin sensitivity and beta-cell function, respectively. Fat was measured by dual-energy X-ray absorptiometry. Fatty liver was diagnosed by ultrasonography and ordinally coded as 0 = none, 1 = light, 2 = moderate, 3 = severe. Proportional-odds logistic regression was used to evaluate the association of NAFLD severity with log(e)ISI and log(e)DI with and without correction for total and truncal fat. RESULTS: The odds of more severe vs. less severe NAFLD decreased for increasing log(e)ISI [odds ratio (OR) 0.40, 95 % CI 0.19-0.84, p < 0.05] and log(e)DI (OR 0.80, 95 % CI 0.69-0.92, p < 0.01). Neither total nor truncal fat had any effect on these associations. CONCLUSION: In morbidly obese women, NAFLD severity is inversely associated with insulin sensitivity and beta-cell function. The association of NAFLD severity with beta-cell dysfunction is stronger than that with insulin resistance.

Psychometric properties of the Fatigue Severity Scale in obese patients.

BACKGROUND: The aim of this study was to examine the psychometric properties of the Fatigue Severity Scale (FSS) to verify whether this instrument is a valid tool to measure fatigue in obese patients, and to examine the prevalence of fatigue in obese patients. METHODS: Before and after a three-week residential multidisciplinary integrated weight reduction program, 220 patients were asked to fill in the questionnaires: FSS, Profile of Mood States (Fatigue-Inertia subscale, POMS-Fatigue, and Vigor-Activity subscale, POMS-Vigor), and the Obesity-Related Well-Being (ORWELL-97). A subsample of 50 patients completed the questionnaire within two days. RESULTS: The prevalence of fatigue using a cut-off value of 4 for the FSS score was 59%. Correlations were found between FSS and POMS-Fatigue and -Vigor scores (r=0.58 and 0.53, respectively). A relation was also found between FSS and ORWELL97 (r=0.52, 0.42 to 0.61). From the factorial analysis only 1 factor was extracted explaining 63% of variance, with factor loading values ranging from 0.71 (item 7) to 0.87 (item 6). Intraclass Correlation Coefficient was 0.89 (0.82 to 0.94), while the agreement as measured using the Standard Error of Measurement was 0.43 (0.36 to 0.54) corresponding to 13% (11 to 17%). Cronbach's alpha values ranged from 0.94 to 0.93. The internal responsiveness of FSS was comparable to the ORWELL97 (Standardized Response Mean=0.50 and 0.44, respectively). CONCLUSIONS: Fatigue is an important and frequent symptom in obese patients and therefore should be routinely assessed in both research and clinical practice. This can be achieved using the FSS, which is a short, simple, valid and reliable tool for assessing and quantifying fatigue in obese patients.

A Metabolomics-Based Investigation of the Effects of a Short-Term Body Weight Reduction Program in a Cohort of Adolescents with Obesity: A Prospective Interventional Clinical Study.

Metabolomics applied to assess the response to a body weight reduction program (BWRP) may generate valuable information concerning the biochemical mechanisms/pathways underlying the BWRP-induced cardiometabolic benefits. The aim of the present study was to establish the BWRP-induced changes in the metabolomic profile that characterizes the obese condition. In particular, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to determine a total of 188 endogenous metabolites in the plasma samples of a cohort of 42 adolescents with obesity (female/male = 32/10; age = 15.94 ± 1.33 year; body mass index standard deviation score (BMI SDS) = 2.96 ± 0.46) who underwent a 3-week BWRP, including hypocaloric diet, physical exercise, nutritional education, and psychological support. The BWRP was capable of significantly improving body composition (e.g., BMI SDS, p < 0.0001), glucometabolic homeostasis (e.g., glucose, p < 0.0001), and cardiovascular function (e.g., diastolic blood pressure, p = 0.016). A total of 64 metabolites were significantly reduced after the intervention (at least p < 0.05), including 53 glycerophospholipids (23 PCs ae, 21 PCs aa, and 9 lysoPCs), 7 amino acids (tyrosine, phenylalanine, arginine, citrulline, tryptophan, glutamic acid, and leucine), the biogenic amine kynurenine, 2 sphingomyelins, and (free) carnitine (C0). On the contrary, three metabolites were significantly increased after the intervention (at least p < 0.05)-in particular, glutamine, trans-4-hydroxyproline, and the octadecenoyl-carnitine (C18:1). In conclusion, when administered to adolescents with obesity, a short-term BWRP is capable of changing the metabolomic profile in the plasma.

Changes in DNA Methylation of Clock Genes in Obese Adolescents after a Short-Term Body Weight Reduction Program: A Possible Metabolic and Endocrine Chrono-Resynchronization.

Circadian rhythms are generated by a series of genes, collectively named clock genes, which act as a self-sustained internal 24 h timing system in the body. Many physiological processes, including metabolism and the endocrine system, are regulated by clock genes in coordination with environmental cues. Loss of the circadian rhythms has been reported to contribute to widespread obesity, particularly in the pediatric population, which is increasingly exposed to chronodisruptors in industrialized society. The aim of the present study was to evaluate the DNA methylation status of seven clock genes, namely clock, arntl, per1-3 and cry1-2, in a cohort of chronobiologically characterized obese adolescents (n: 45: F/M: 28/17; age ± SD: 15.8 ± 1.4 yrs; BMI SDS: 2.94 [2.76; 3.12]) hospitalized for a 3-week multidisciplinary body weight reduction program (BWRP), as well as a series of cardiometabolic outcomes and markers of hypothalamo-pituitary-adrenal (HPA) function. At the end of the intervention, an improvement in body composition was observed (decreases in BMI SDS and fat mass), as well as glucometabolic homeostasis (decreases in glucose, insulin, HOMA-IR and Hb1Ac), lipid profiling (decreases in total cholesterol, LDL-C, triglycerides and NEFA) and cardiovascular function (decreases in systolic and diastolic blood pressures and heart rate). Moreover, the BWRP reduced systemic inflammatory status (i.e., decrease in C-reactive protein) and HPA activity (i.e., decreases in plasma ACTH/cortisol and 24 h urinary-free cortisol excretion). Post-BWRP changes in the methylation levels of clock, cry2 and per2 genes occurred in the entire population, together with hypermethylation of clock and per3 genes in males and in subjects with metabolic syndrome. In contrast to the pre-BWRP data, at the end of the intervention, cardiometabolic parameters, such as fat mass, systolic and diastolic blood pressures, triglycerides and HDL-C, were associated with the methylation status of some clock genes. Finally, BWRP induced changes in clock genes that were associated with markers of HPA function. In conclusion, when administered to a chronodisrupted pediatric obese population, a short-term BWRP is capable of producing beneficial cardiometabolic effects, as well as an epigenetic remodeling of specific clock genes, suggesting the occurrence of a post-BWRP metabolic and endocrine chronoresynchronization, which might represent a "biomolecular" predictor of successful antiobesity intervention.

Responsiveness of the Italian version of the Pediatric Quality of Life Multidimensional Fatigue Scale in adult inpatients with obesity.

This study aimed to evaluate the responsiveness of the Italian version of the Paediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL-MFS) to changes in BMI, fatigue and depressive symptoms in adult inpatients with obesity. 198 adults (81% female, mean age = 44.7 years) with obesity completed the PedsQL-MFS, the Fatigue Severity Scale (FFS) and the Centre for Epidemiologic Studies Depression Scale (CESD) before and after completing a 3-week body weight reduction program. Internal responsiveness was measured via paired t-tests, standardized mean response (SMR) and Glass's delta (d). Changes in FFS, CESD and BMI were used as anchors to categorize participants as "improved", "unchanged" or "deteriorated". External Responsiveness was assessed by comparing mean post-intervention PedsQL-MFS scores across change groups, adjusting for pre-intervention PedsQL-MFS scores and in area-under-curve (AUC) analysis. PedsQL-MFS Total, Sleep/Rest Fatigue and Cognitive Fatigue scores demonstrated significant reductions in response to an established body weight reduction program. Post-intervention PedsQL-MFS scale scores were lower among those who had improved on the CESD and FSS than among those whose CESD and FSS scores had not significantly changed. There was no difference in PedsQL-MFS scale scores according to whether participants had reduced their BMI by at least 5%. AUC analyses indicated that change in PedsQL-MFS scores was somewhat more predictive of improvement in CESD than FSS scores. The Italian version of the PedsQL-MFS demonstrated both internal and external responsiveness. It appeared more sensitive to improvement than deterioration in fatigue symptoms and its sensitivity to deterioration in depressive symptoms and weight loss could not be evaluated in the present study as there was no reliable deterioration in CESD scores and weight loss was modest. Future studies should include a control group to assess the sensitivity of the PedsQL-MFS more thoroughly.

Differences in soleus H-reflex to M-wave ratio between obese and non-obese individuals.

BACKGROUND: The aim of this cross-sectional comparative study was to investigate potential differences in soleus H-reflex to M-wave ratio between obese and non-obese individuals under different postural constraints. METHODS: A total of 23 obese individuals and 23 matched non-obese controls took part in the study. The maximal soleus H-reflex to M-wave ratio (peak-to-peak amplitude) was quantified in three different conditions: seated at rest, seated with a light contraction of the plantar flexors and during bipedal quiet standing. FINDINGS: Soleus H-reflex to M-wave ratio was significantly higher in obese than in non-obese individuals in all the experimental conditions (p < 0.01). INTERPRETATION: Obese individuals showed larger normalized soleus H-reflex responses than their non-obese counterparts, probably as a reflect of long-term neurophysiological adaptations to excessive body weight and postural demands.

The ACTyourCHANGE in Teens Study Protocol: An Acceptance and Commitment Therapy-Based Intervention for Adolescents with Obesity: A Randomized Controlled Trial.

This Randomized Controlled Trial [(RCT) aims to evaluate the effectiveness of a brief Acceptance and Commitment Therapy (ACT)-based intervention combined with treatment as usual (TAU) compared to TAU only in improving psychological conditions in a sample of adolescents with obesity (body mass index, BMI > 97th percentile for age and sex) within the context of a wider multidisciplinary rehabilitation program for weight loss. Fifty consecutive adolescents (12-17 years) of both genders with obesity will be recruited among the patients hospitalized in a clinical center for obesity rehabilitation and randomly allocated into two experimental conditions: ACT + TAU vs. TAU only. Both groups will attend a three-week in-hospital multidisciplinary rehabilitation program for weight loss. The ACT + TAU condition comprises a psychological intervention based on ACT combined with a standard psychological assessment and support to the hospitalization. The TAU comprises the standard psychological assessment and support to the hospitalization. At pre- to post-psychological intervention, participants will complete the Avoidance and Fusion Questionnaire for Youth, the Psychological Well-Being Scale, the Depression Anxiety Stress Scale, the Difficulties in Emotion Regulation Scale, and the Emotional Eating subscale of the Dutch Eating Behavior Questionnaire to assess psychological well-being as the primary outcome and experiential avoidance, psychological distress, emotional dysregulation, and emotional eating as secondary outcomes. Repeated-measures ANOVAs (2 × 2) will be conducted. The study will assess the effectiveness of a brief ACT-based intervention for adolescents with obesity in improving their psychological conditions by targeting specific core processes of the ACT framework (openness, awareness, and engagement). Future directions of the study will assess whether these psychological processes will contribute to addressing long-term weight loss.

A 3-Week Multidisciplinary Body Weight Reduction Program Improves Body Composition and Lower Limb Power Output in 3,778 Severely Obese Children and Adolescents.

The aim of the present study was to investigate the effects of a 3-week in-hospital body weight reduction program (BWRP), entailing moderate energy restriction, physical activity, psychological counseling and nutritional education, on body composition and lower limb muscle power (LLP) output in obese children and adolescents. Three thousand seven hundred seventy-eight obese [BMI: 36.2 ± 5.9 kg⋅m-2; fat mass (FM): 42.7 ± 4.0%] children and adolescents (2,318 girls and 1,460 boys, aged 8-18 year) participated in this study. Before (T0) and after the end of the BWRP (21st day, T21), body composition was assessed by an impedancemeter and LLP by the Margaria stair climbing test. Body mass (BM) and FM significantly decreased in girls (-4.8 and -7.1%, p < 0.001) and in boys (-5.5 and -9.3%, p < 0.001) after 3-week BWRP, while fat-free mass (FFM) did not change significantly in both genders. LLP expressed in absolute values (W) significantly increased in girls (by mean 6.4% from age 13 to 18 year, P < 0.001) and in boys (by mean 7.2% from age 12 to 18 year, P < 0.001). LLP normalized to BM (W⋅kg-1BM) significantly increased in girls (by mean 11.3%, P < 0.001) and boys (by mean 12.6%, P < 0.001) from age 9 to 18 year. As well, LLP normalized to FFM (W⋅kg-1FFM) significantly increased in girls (by mean 9.1% from age 9 to 18 year, P < 0.001) and in boys (by mean 10.1% from age 10 to 18 year, P < 0.001). In conclusion, 3-week BWRP induces a significant decrease in FM and maintenance in FFM in obese children and adolescents, these effects being also associated with a significant increase of LLP both in absolute terms and when normalized to the BM or FFM.

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.

External Validation of Equations to Estimate Resting Energy Expenditure in 2037 Children and Adolescents with and 389 without Obesity: A Cross-Sectional Study.

We performed an external cross-validation study of 10 equations to estimate resting energy expenditure (REE) in 2037 children with and 389 without obesity. Inclusion criteria were Caucasian ethnicity, age ≤ 18 years, and availability of REE. REE was measured using indirect calorimetry. The correct classification fraction (CCF) of an equation was defined as the fraction of subjects whose estimated REE was within 10% of measured REE. The Molnár equation was the most accurate REE prediction equation with CCFs of 0.70 (95% CI 0.65 to 0.76) in girls without obesity, 0.64 (95% CI 0.61 to 0.66) in girls with obesity, 0.76 (95% CI 0.67 to 0.83) in boys without obesity, and 0.66 (95% CI 0.63 to 0.69) in boys with obesity. The Mifflin equation was the second most accurate equation with CCFs of 0.67 (95% CI 0.61 to 0.73) in girls without obesity, 0.61 (95% CI 0.58 to 0.64) in girls with obesity, 0.75 (95% CI 0.66 to 0.82) in boys without obesity, and 0.66 (95% CI 0.63 to 0.69) in boys with obesity.

Association of serum lipids with ß-cell function in obese children and adolescents.

Few data are available on the association between serum lipids and insulin secretion (ISEC) in children. We evaluated the association of triglycerides (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) with ISEC in 1150 non-diabetic obese children and adolescents using multivariable robust median regression. The following models were employed: (1) IGI or incAUCR as the ISEC response variable; (2) QUICKI, OGIS, the Stumvoll index or the Matsuda insulin sensitivity index as the insulin sensitivity (ISEN) predictor; (3) TG, HDL-C and LDL-C as the predictors of interest; (4) 120-min glucose, age, sex and body mass index as confounders. LDL-C and TG were not associated with ISEC in any model. In three out of four IGI models, an increase of 1 interquartile range (IQR) of HDL-C was associated with a decrease of median incAUCR ranging from -9 (robust 95% CI -17 to -2) to -8 (-14 to -1) pmol/mmol. In two out of four incAUCR models, an increase of 1 IQR of HDL-C was associated with a decrease of median IGI ranging from -8 (-15 to -1) to -7 (-11 to -2) pmol/mmol. TG and LDL-C are not associated and HDL-C is inversely associated with ISEC in obese children and adolescents.

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.