Background: While sphingolipid alterations in obesity and metabolic syndrome (MS) have been extensively studied in plasma, their intracellular regulation within immune cells remains poorly characterized. Here, we introduce a PBMC-based sphingolipidomic approach that provides a novel immunometabolic perspective beyond traditional analyses of circulating lipids. Methods: Targeted sphingolipidomics was performed in peripheral blood mononuclear cells (PBMCs) from normal-weight healthy (NWH) subjects, and patients with essential obesity (EO) or MS. Multivariate integration (principal component analysis [PCA], hierarchical clustering, and partial least squares discriminant analysis [PLS-DA]) was combined with selected univariate models to explore lipid patterns and associations with cardiometabolic variables. Results: PBMC profiling identified a selective intracellular sphingolipid signature, with 10 species significantly altered across groups (FDR < 0.05), including ceramides, dihydroceramides, glycosphingolipids, and ceramide ratio indices. PCA showed that the first two components explained ~72% of total variance, with PC2 driving group separation. EO and MS displayed partial overlap, consistent with a shared metabolic phenotype, while both differed from NWH. Multivariate models highlighted ceramide ratios (e.g., CER16/24, and CER18/24) as key discriminators. Associations with cardiometabolic variables were limited and modest (adjusted R2 ≈ 0.06-0.09), indicating that lipid alterations reflect integrated metabolic dysregulation rather than single clinical drivers. Conclusions: PBMC-based sphingolipidomics reveals a distinct intracellular immunometabolic remodeling in EO and MS, capturing aspects not detectable in plasma. These findings support the relevance of immune cell lipid profiling as a potential source of integrative biomarkers and provide insight into immune-metabolic crosstalk underlying metabolic disease.

Background: Anorexia Nervosa (AN) triggers profound metabolic and psychological adaptations during adolescence. This study investigated the relationships between resting energy expenditure (REE), body composition, physical activity (PA), and specific psychometric phenotypes in adolescent girls with AN compared to healthy, normal-weight (NW) peers. Methods: Sixteen adolescent girls with severe AN (16.1 ± 1.2 year) and 16 age-matched NW controls (15.6 ± 1.5 year) underwent clinical evaluations: anthropometry, bioelectrical impedance analysis for fat-free mass (FFM) and fat mass (FM), indirect calorimetry for REE, the short-form International Physical Activity Questionnaire (IPAQ), and the Eating Disorder Inventory-3 (EDI-3). Results: Girls with AN exhibited significantly lower BMI (-20.3%, ES: 1.94, large), FFM (-18.3%, ES: 1.92, large), and FM (-25.7%, ES: 0.79, medium) than controls (p < 0.003). Absolute REE was drastically lower (-40.4%, ES: 3.53, large, p < 0.001). This hypometabolic state persisted after adjusting REE for body weight (-34.9%) or FFM (-32.5%, p < 0.001), consistent with adaptive thermogenesis. The AN group displayed resting hypotension and 79.0% (ES: 1.84, large, p < 0.001) lower total PA energy expenditure due to a lack of structured moderate-to-vigorous exercise; however, walking expenditure did not differ. Psychometrically, the AN cohort showed significantly higher (p < 0.001) values for drive for thinness (+316.9%, ES: 3.16, large), body dissatisfaction (+232.3%, ES: 2.30, large), and severe general psychological maladjustment, including higher interoceptive deficits (+148.2%, ES: 1.26, large). Conclusions: Adolescents with AN exhibit profound metabolic suppression via adaptive thermogenesis, together with an apparent dissociation between walking-related activity and hypotension. Since cognitive distortions and distress vary independently of anthropometric severity, clinical recovery must extend beyond nutritional rehabilitation; targeted psychotherapy may therefore be necessary to address persistent psychological maladjustment.

Background/Objectives: Pediatric obesity is closely associated with metabolic syndrome (MetS), a condition linked to increased cardiometabolic risk. Early identification of high-risk individuals remains challenging. This study aimed to evaluate the diagnostic performance of selected anthropometric, metabolic dysfunction and insulin resistance indexes for identifying MetS in children and adolescents with obesity. Methods: In this retrospective, cross-sectional, single-center study, 758 children and adolescents with obesity (mean age 14.8 ± 2.1 years; 59.9% females) hospitalized for a body weight-reduction program were included. MetS was defined according to International Diabetes Federation criteria, in which central obesity is a mandatory diagnostic component. The triglyceride–glucose (TyG), TyG–waist circumference (TyG-WC), body adiposity index (BAI), fasting glucose-to-insulin ratio (FGIR), and quantitative insulin sensitivity check index (QUICKI) were calculated. Receiver operating characteristic curve analysis was used to assess their discriminative ability. Results: The prevalence of MetS was 27.8% and was significantly higher in males than females (34.9% vs. 23.1%, p < 0.0001). TyG and TyG-WC showed the best discriminative performance (AUC 0.75 and 0.76, respectively), although with only moderate sensitivity and specificity. FGIR and QUICKI demonstrated lower accuracy (AUC 0.64 and 0.63), whereas BAI showed no discriminative ability (AUC 0.48). These findings were consistent across sexes, although sex-specific differences in both MetS prevalence and optimal cut-off values were observed. Correlation analyses confirmed moderate associations between TyG-based indexes and MetS, whereas other indexes showed weaker relationships. Conclusions: In the present cohort of children and adolescents with obesity, TyG and TyG-WC showed the best performance in identifying MetS compared with the other evaluated indexes. However, their performance remained moderate, and the proposed cut-off values require validation in independent populations. These indexes may represent simple supportive screening and risk-stratification tools but should be used alongside comprehensive clinical assessment and established diagnostic criteria rather than as stand-alone diagnostic measures.

Prader-Willi syndrome (PWS; MIM# 176270) is a rare neurodevelopmental disorder characterized by clinical manifestations across multiple body systems. PWS represents an atypical form of obesity-associated metabolic disease in which extreme adiposity coexists with a comparatively attenuated risk of insulin resistance and hepatic complications. The genetic basis of PWS leads to impaired lipid storage and oxidation capacity in adipocytes, with downstream consequences for hepatic lipid burden. Systemic lipidomic and metabolomic profiling further supports the existence of a distinct metabolic signature in PWS, showing consistent qualitative alterations in circulating phospholipids that may, in turn, influence hepatic lipid export and the risk of steatosis. Hepatic involvement in PWS seems to be shaped by intrinsic alterations in lipid handling and endocrine signaling rather than by adiposity. Finally, metabolic dysfunction-associated steatotic liver disease (MASLD) remains less prevalent in PWS. Among the currently available models derived from induced pluripotent stem cells (iPSCs), hepatocyte-like cells (HLCs) and iPSC-derived organoids, have emerged as valuable tools for investigating rare genetic liver disorders and as powerful strategies to dissect tissue-specific mechanisms underlying PWS phenotype, because they bridge the gap between molecular epigenetic mechanisms and organism-level metabolic phenotypes in PWS. Their ability to capture patient-specific epigenetic regulation and tissue-specific metabolic dysfunction positions them as indispensable tools for advancing both mechanistic understanding and therapeutic development in PWS.

Background: Sarcopenic obesity (SO) is a clinically relevant but often under-recognized condition in older adults. This study examined whether obesity severity and body fat distribution are associated with physical capacity, functional autonomy and health-related quality of life in a sex-specific manner. Methods: In this observational case–control study with cross-sectional assessments, 45 older obese adults (OB; 27 men and 18 women) and 40 non-obese (NOB) comparison participants (18 men and 22 women), aged 65–85 years, underwent anthropometric assessment, bioelectrical impedance analysis, geometric body shape indexing, physical performance testing, autonomy assessment, physical activity evaluation and health-related quality-of-life assessment. SO was classified using a study-specific operational application of the ESPEN/EASO framework based on excess adiposity, impaired muscle function, and BIA-derived skeletal muscle mass adjusted for body mass. Results: Using this operational framework, all participants in the OB group were classified as presenting an SO phenotype. OB men showed substantially greater visceral adipose tissue mass than OB women (+106.5%, ES: 1.27, large, p < 0.001) and a higher A body shape index-associated relative risk (+27.9%, ES: 0.82, large, p < 0.001). Conversely, OB women showed more severe mobility impairment than OB men, with lower performance in the 8-Foot Up-and-Go (−22.9%, ES: 0.66, medium, p < 0.001) and 6-Min Walk test (−23.4%, ES: 0.64, medium, p < 0.001) and slightly lower basic autonomy. Health-related quality of life was significantly reduced only in OB men (−10.8%, ES: 1.07, large, p < 0.001) than NOB. Conclusions: In this clinical sample, an operational SO phenotype was identified among older OB adults and exhibited divergent sex-specific profiles. Men showed a predominantly geometric visceral risk phenotype and poorer perceived health status, whereas women showed more pronounced impairment in mobility and basic functional autonomy. These findings support sex-differentiated, multidisciplinary rehabilitation strategies in older adults with obesity.

Background: Sex-related differences in insulin sensitivity during adolescence remain incompletely understood, particularly in the context of obesity. Whether these differences reflect variations in basal insulin resistance or dynamic insulin responses remains unclear. Objective: To investigate sex differences in glucose and insulin responses during the oral glucose tolerance test (OGTT) and to explore mechanisms underlying potential dissociation between glycemic and insulinemic profiles. Methods: A cross-sectional analysis of 753 adolescents with obesity who underwent a standard oral glucose tolerance test (OGTT). Plasma glucose and insulin were measured at fasting and at 30, 60, 90, and 120 min. Mixed-effects models were used to examine glucose and insulin trajectories over time, including sex-by-time interactions, and to adjust for body mass index standard deviation score (BMI_SDS), pubertal stage (Tanner), metabolic syndrome (MetS), and body composition (resistance index). Multiple linear regression models were fitted to assess associations of sex with HOMA-IR, HOMA-β, total area under the curve (AUC), and phase-specific insulin AUCs. Results: Glucose trajectories during OGTT were similar between sexes, with no significant sex or sex-by-time interaction effects after adjustment. In contrast, insulin trajectories differed significantly by sex (sex-by-time interaction β = -0.10, p < 0.001). Boys exhibited higher baseline insulin levels and greater total insulin exposure (β = -11.2, p < 0.001), independent of BMI_SDS, pubertal stage, MetS, and body composition. Sex differences were sustained across all OGTT phases. HOMA-IR did not differ by sex, whereas HOMA-β showed a sex-related difference. BMI was positively associated with both basal and dynamic insulin measures. Conclusions: In adolescents with obesity, sex differences are characterized by altered dynamic insulin responses rather than differences in glycemic control. Boys exhibit greater compensatory insulin exposure during glucose challenge, independent of BMI-based adiposity, BIA-derived body composition and pubertal development.

Background:Sarcopenic obesity (SO) is characterized by the coexistence of sarcopenia and excess adipose tissue, increasing the risk of falls and related adverse outcomes in older adults. However, diagnostic criteria for SO remain inconsistent, warranting further investigation. This study aimed to examine the association between SO, defined according to the criteria proposed by the 2022 European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO), and the history of falls among hospitalized older Italian adults. Methods:This cross-sectional study included 90 older Italian adults (≥ 60 years) with severe obesity (body mass index ≥ 35 kg/m2). The exposure variable, SO, was defined by the concomitant presence of reduced muscle function, high fat mass, and low muscle mass adjusted for body weight. Muscle function was assessed using the Five-Times Sit-to-Stand (5×STS) test and handgrip strength (HGS). Fat mass percentage (FM%) was measured using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA). Appendicular muscle mass (AMM/W) and skeletal muscle mass (SMM/W), both adjusted for body weight, were assessed using DXA and BIA, respectively. Four diagnostic definitions of SO were analyzed according to the following combinations of tests and instruments: 1) 5×STS + FM% DXA + AMM/W, 2) 5×STS + FM% BIA + SMM/W, 3) HGS + FM% DXA + AMM/W, and 4) HGS + FM% BIA + SMM/W. The outcome was self-reported falls in the past year. Multivariable logistic regression models were adjusted for sex, age, education, marital status, fall-related multimorbidity, alcohol consumption, and regular physical activity. Results:Significant associations between SO and falls were found only when muscle function was assessed using HGS, regardless of the method used to estimate FM% and muscle mass. In adjusted analyses, participants classified as having SO according to combinations HGS + FM% BIA + SMM/W and HGS + FM% DXA + AMM/W had approximately almost fourfold (OR=3.61; 95% CI: 1.28-10.19) and sixfold (OR=6.03; 95% CI: 1.80-20.23) higher odds of reporting falls in the previous year, respectively, when compared to those without SO considering the same diagnostic tests. Conclusion:SO defined by low HGS combined with high FM% and low muscle mass adjusted for body weight-whether measured using DXA or BIA-was associated with greater odds of falls in older Italian adults. These findings support the use of muscle strength-based definitions of SO when evaluating fall risk in this population.

BackgroundPediatric obesity is characterized by substantial metabolic heterogeneity, including adiposity, insulin resistance, inflammation, and energy metabolism. Traditional categorical classifications may inadequately capture this complexity. Objective: To identify clinically meaningful metabolic phenotypes using unsupervised clustering and to compare the statistical performance and clinical interpretability of two- and three-cluster solutions.MethodsIn this cross-sectional study, 758 children and adolescents with obesity underwent anthropometric, biochemical, and indirect calorimetry assessments. Fat-free mass was estimated using validated bioimpedance-based equations, and fat-free mass index (FFMI) was standardized before clustering. K-means clustering (k = 2 and k = 3) was performed using FFMI z-score, BMI-SDS, HOMA-IR, triglycerides, and HDL-cholesterol. Cluster validity was assessed using the Silhouette, Elbow, Davies–Bouldin index, Calinski–Harabasz index, and Gap statistic methods. Validation employed variables not included in clustering, such as glucose-insulin dynamics, inflammatory and hepatic markers, blood pressure, respiratory quotient, and resting energy expenditure (REE). Group comparisons were performed using Kruskal–Wallis and Dunn’s post-hoc tests with false discovery rate correction.ResultsBoth clustering solutions demonstrated significant separation across metabolic domains. The two-cluster model identified metabolically favourable and unfavourable phenotypes differing in adiposity, insulin resistance, inflammatory burden, hepatic markers, blood pressure, and REE. The three-cluster solution revealed a more granular metabolic stratification with an intermediate phenotype characterized by partial metabolic impairment. Validation confirmed robust differences across physiological variables (all FDR-adjusted p < 0.05). Although the two-cluster solution showed slightly superior internal validity, the three-cluster model provided greater clinical granularity and phenotypic resolution.ConclusionsUnsupervised clustering identified biologically coherent metabolic phenotypes in pediatric obesity. While the two-cluster solution provided statistically robust stratification, the three-cluster configuration captured a broader spectrum of metabolic heterogeneity and risk profiles, supporting the application of higher-resolution phenotyping approaches in pediatric endocrinology and metabolic risk assessment.

BackgroundA growing body of literature has emphasized the role of worry and rumination in eating disorders (EDs). According to the metacognitive model, worry and rumination are maintained by dysfunctional metacognitive beliefs. Although metacognitive beliefs have been investigated in adults with EDs, their role in adolescents with EDs remains underexplored. The present exploratory study aimed to examine the specific association among worry, rumination, and metacognitive beliefs and eating disorder symptomatology in adolescents with AN.MethodsThirty Italian female adolescents (mean age ± SD: 15.387 ± 1.35 years, mean Body Mass Index (BMI): 16.34 ± 2.5 kg/m2) completed a self-report survey composed of the Penn State Worry Questionnaire (PSWQ), the Ruminative Response Scale (RRS), the Metacognitions Questionnaire – 30 (MCQ-30), and the Eating Disorder Inventory – 3 (EDI-3).ResultsThus, Model 1, including RRS and PSWQ, was significant (F = 17.5, p<0.001) and explained 57% of the variance (R² = 0.574). Within this model, RRS was the only significant predictor (p = 0.019) of the Eating Disorder Risk Composite (EDRC) of EDI-3, indicating that higher rumination scores were associated with greater eating disorder symptomatology. Once MCQ was entered as a predictor of EDRC, there was no significant incremental variance compared with Model 2 (ΔR² = 0.0034, p = 0.658), even though the model remained significant overall (F = 11.4, p < 0.001). The final model explained 58% of variance (R² = 0.578; Cohen’s f2 = 1.37).ConclusionRumination was significantly associated with eating disorder symptomatology. Although worry showed strong positive associations with eating disorder symptomatology at the correlational level, it did not maintain an independent role once rumination was included in the regression model. The final model showed a very large effect size (Cohen’s f² = 1.37), suggesting strong associations between predictors and eating disorder symptoms in the present sample. However, this estimate should be interpreted cautiously, given the limited sample size and the exploratory nature of the analysis. Contrary to our expectations, metacognitive beliefs did not significantly explain the variance of eating disorder symptomatology. This finding may reflect the more proximal role of RNT in explaining the variance in eating disorder symptomatology, or alternatively, the possibility that only specific metacognitive domains—rather than overall metacognitive functioning—are relevant in this population.

Background/Objectives: Existing literature has consistently identified perfectionism as a core feature of anorexia nervosa (AN). However, much of the research has focused primarily on its association with eating disorder-related symptoms. At the same time, less attention has been paid to understanding how perfectionism affects the overall psychological functioning of individuals with eating disorders, and in particular AN. The present study aimed at investigating the association between perfectionism and both eating disorder-specific symptomatology and general psychological symptoms in a sample of young adult Italian women diagnosed with AN. Methods: Thirty-five Italian females diagnosed with AN (mean age ± SD: 21.9 ± 4.18 years; mean body mass index: body mass index ± SD: 14.5 ± 1.77 kg/m2) were consecutively recruited at the Division of Eating and Nutrition Disorders, Istituto Auxologico Italiano, IRCCS, Piancavallo-Verbania, a third-level clinical centre for the rehabilitation of obesity and eating disorders located in northern Italy. Once informed about the research, screened for inclusion/exclusion criteria, and enrolled, participants were asked to complete the Eating Disorder Inventory—third edition, the Symptoms Checklist-90 revised, and the Frost Multidimensional Perfectionism Scale to collect demographic and clinical variables of interest for the study. Three hierarchical linear regression models were tested to explore the role of perfectionism in both eating disorder-specific symptomatology and general psychological symptoms. Results: The analyses showed a significant influence of perfectionism in all tested models, suggesting that perfectionism was significantly associated with both eating disorder-specific symptomatology and general psychological symptoms in a sample of young adult Italian women diagnosed with AN. Conclusions: The findings of this study provide further support for the role of perfectionism in the psychopathology of eating disorders, particularly among young adult women with AN. Consistent with prior research, perfectionism was associated with both disorder-specific symptoms and broader psychological symptoms. Notably, its association remained robust even after controlling for key variables such as age and body mass index, underscoring its potential as an independent risk factor.

Background/Objectives: The study aimed to investigate the presence of worry, rumination, and metacognitive beliefs in adolescents with maladaptive eating behaviours. Methods: The study involved 37 adolescents (10 males, 27 females, mean age ± SD: 15.4 ± 1.53 years) with obesity (Body Mass Index, BMI > 97th centile) associated with binge eating disorder (BED) (BES score ≥ 17) and 30 age-matched adolescents (13 males, 17 females, mean age ± SD: 15.2 ± 1.98 years) with essential obesity (i.e., without BED, BES score < 17). Participants completed self-report questionnaires-Penn State Worry Questionnaire (PSWQ), Ruminative Response Scale (RRS), Anger Rumination Scale (ARS), and Metacognitions Questionnaire for Children (MCQ-C)-to assess binge eating, worry, rumination, and metacognitive beliefs, respectively. Results: Patients with obesity and BED showed higher scores on the PSWQ (p = 0.006), RRS (p < 0.001), ARS (p < 0.001), negative Metaworry (p = 0.011), and total MCQ-C (p = 0.027) than those with essential obesity, with a medium-to-large effect size, indicating that the differences between subgroups were meaningful. Conclusions: Our findings highlight that BMI alone is not associated with metacognitive processes and beliefs. The presence of BED in adolescents with obesity is linked to increased levels of worry, rumination, and maladaptive metacognitive beliefs, in comparison with age-matched adolescents with essential obesity. The results of the study underline the need for different psychological approaches in these clinical conditions going forward.

Background: Recombinant human growth hormone (rhGH) replacement therapy, administered to children with growth hormone deficiency (GHD), exerts pleiotropic effects on growth, metabolism, and tissue functions. Extracellular vesicles (EVs) are emerging mediators of inter-organ communication, but the effects of rhGH therapy on EV release in humans have not yet been investigated. Methods: In a preliminary prospective clinical study, children with GHD (n = 10; F/M = 5/5; age: 11.0 ± 2.7 years) were treated with rhGH for 6 months. Plasma samples were collected at baseline (T0) and after treatment (T6) to characterize the size distribution and tissue-derived composition of circulating EVs. Total EVs and EV subpopulations derived from monocytes/macrophages (CD14+), adipose tissue (FABP+), skeletal muscle (SCG+), endothelium (CD62E+), and platelets (CD42A+) were analyzed. Clinical, auxological/auxometric, and biochemical/metabolic parameters were assessed in parallel. Statistical methods included longitudinal analyses, interaction models, and adjustments for relevant covariates, including insulin-like growth factor 1 (IGF-1) and osteocalcin. Results: After 6 months of rhGH therapy, significant improvements in height velocity (cm/year and SDS) were observed, accompanied by increased circulating IGF-1 and osteocalcin levels. Hormone therapy induced no size-dependent changes in (total) EVs. Significant increases in CD14+ and FABP+ EVs were observed after treatment, without affecting the other tissue-derived EVs. Interaction analyses revealed that children with more severe GHD exhibited a stronger vesiculogenic response to rhGH. Furthermore, specific tissue-derived EVs were associated with metabolic/biochemical and auxological/auxometric parameters, including lipids, insulin resistance, and growth-related measures. Conclusions: When administered for six months, rhGH therapy seems to selectively change tissue-derived composition of circulating EVs in GHD children, particularly those derived from immune cells and adipose tissue. These preliminary findings suggest that EVs might represent an adjunctive component of GH-dependent inter-organ communication and might serve as biomarkers of treatment response and disease severity in pediatric endocrinology.

Background: Anorexia nervosa is an eating disorder characterised by distorted eating behaviour, physical and mental health problems, and the highest mortality rate among psychiatric disorders. Although anorexia nervosa appears to be associated with alterations in the spine, studies investigating the characteristics of spinal postures and mobility in individuals with anorexia nervosa are scarce to date. The present study aims to examine the relationship between anorexia nervosa and spinal posture and mobility by comparing people with anorexia nervosa to age-matched, normal-weight controls. Methods: Spinal posture and mobility were evaluated using a radiation-free back scan, the Idiag M360 (Idiag, Fehraltorf, Switzerland). Between-group differences were assessed using a two-way analysis of variance. Results: Adult females suffering from anorexia nervosa exhibited reduced lumbar [difference between groups (Δ) = 10.5°, 95% CI 4.6°–16.5°, p < 0.001] and thoracic (Δ = 8.8°, 95% CI 2.4°–15.2°, p = 0.007) curvatures compared to normal-weight controls. The only difference observed in spinal movements between the two groups was thoracic flexion, which was greater in individuals with anorexia nervosa (Δ = 8.4°, 95% CI 2.1°–14.4°, p = 0.009). Conclusions: These findings emphasise the need to consider spinal posture and thoracic mobility in the musculoskeletal assessment of anorexia nervosa. Interventions aimed at improving spinal postures may help to develop effective rehabilitative strategies for addressing spinal problems associated with anorexia nervosa and thus contributing to counteract the possible further worsening with advancing age.

Background. Anorexia nervosa (AN) is a metabolic-psychiatric disease, in which, besides an extremely low body weight, there is a paradoxical dyslipidemia. Objectives. The aims of the present study were (1) to carry out a sphingolipidomic profiling in a group of women with AN (n = 28; body mass index [BMI]: 15.54 [13.96-16.32] kg/m2) compared to a normal-weight healthy (NWH) group (n = 30; BMI: 22.05 [19.67-23.72] kg/m2), and (2) to correlate plasma levels of single or total sphingolipids with parameters related to body composition, cardiovascular function, glucometabolic homeostasis, and lipoprotein metabolism. Results. Age, weight, BMI, fat mass (FM) (%), and fat-free mass (FFM) (kg) were significantly lower in women with AN than in the NWH group. Women with AN exhibited lower values of both systolic and diastolic blood pressure than the NWH group. Glucose, insulin, and HOMA-IR were significantly lower in women with AN than in the NWH group. Finally, C-reactive protein (CRP) was significantly higher in NWH women than in those with AN. Among all the sphingolipid species evaluated, 16 were significantly increased in AN (single species or whole family of summed species), while 6 were decreased. The highest significant correlations of sphingolipidomic profiling were mainly concentrated within parameters related to body composition. Conclusions. Women with AN have a specific sphingolipidomic profile that could hopefully serve as a marker for monitoring treatment effectiveness.

Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can be measured through different methods, including the age-related epigenetic modifications of DNA. Objective: The present study aimed to evaluate the biological (epigenetic) age and age acceleration in a group of growth hormone (GH)-deficient (GHD) children (F/M = 5/5; age: 11.0 ± 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025–0.035 mg/kg. Results: Treatment with rhGH significantly increased height velocity and circulating insulin-like growth factor 1 (IGF-1) levels. Biological and chronological ages were significantly correlated at baseline and after 6 months of rhGH replacement therapy. Treatment with rhGH reduced age acceleration, an effect that became significant only after adjustment for IGF-1. In a linear regression model for longitudinal data, after adjustment for rhGH treatment, age acceleration was significantly associated with IGF-1 levels, an effect missing when considering the interaction rhGH treatment × age acceleration at 6 months of rhGH treatment. Conclusions: (rh)GH, when administered to GHD children, exerts anti-ageing effects, which become evident after removal of the presumably pro-ageing effects of IGF-1.

PurposeThe aetiology of metabolic syndrome (MetS) in young people involves a complex interplay between lifestyle, body composition, and cardiometabolic risk factors. The present study aimed to explore the relationships between anthropometric characteristics, body composition, cardiometabolic parameters and resting substrate metabolism in the development of MetS in severely adolescents with obesity.MethodsSeven hundred and thirty adolescents with obesity (mean age: 14.6 ± 2.1 years, BMI > 97th percentile for gender and age) were included in this study. Body composition analysis was obtained using tetrapolar bioelectrical impedance analysis (BIA), while resting substrate oxidation was measured using an indirect calorimeter.ResultsMetS was present in 27% of the participants. Compared to those without MetS, adolescents with MetS had significantly higher body mass (+15 kg, p < 0.001), fat-free mass (FFM; +6 kg, p < 0.001), fat mass (+9 kg, p < 0.001), carbohydrate oxidation at rest (CHO; +0.02 g·min−1, p = 0.015), and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; +0.8, p < 0.001). In adjusted-univariate logistic regression, HOMA-IR (OR: 1.22; 95% CI: 1.12–1.34, p < 0.001) was associated with higher odds of MetS. Conversely, higher FFM percentage (OR: 0.96; 95% CI: 0.93–0.99, p = 0.003) and HDL cholesterol levels (OR: 0.83; 95% CI: 0.81–0.86, p = 0.003) were protective.ConclusionIn adolescents with severe obesity, resting carbohydrate oxidation and HOMA-IR emerged as independent risk factors for MetS, offering additional insight beyond conventional anthropometric and lipid indicators. Conversely, higher FFM and HDL cholesterol levels appeared to exert a protective effect. These findings underscore the importance of incorporating metabolic and body composition variables into MetS risk models and support the promotion of targeted interventions, such as endurance and resistance training, to address modifiable risk factors and reduce the likelihood of developing MetS.

Background: Prader–Willi syndrome (PWS) is a rare genetic disorder mapping to the imprinted 15q11-13 locus, specifically at the paternally expressed snord116 region, which has been implicated in controlling epigenetic mechanisms. Some aspects of the PWS-related clinical phenotype, such as the high mortality rate in adulthood, might be attributed to accelerated epigenetic ageing. Objectives: The aim of the present case–control study was to evaluate epigenetic age, age acceleration, vascular age (VA), and vascular ageing in adults with PWS (n = 24; F/M = 11/13; age = 36.8 [26.6; 45.3] years; body mass index, BMI = 36.8 [33.9; 44.8] kg/m2), compared with a sex- and age-matched group of subjects with essential obesity (EOB) (n = 36; F/M = 19/17; age = 43.4 [30.6; 49.5] years; BMI = 44.8 [41.2; 51.7] kg/m2). Results: In subjects with PWS, there was a younger epigenetic age and a lower age acceleration than in subjects with EOB. No differences were found between VA and vascular ageing in the two groups. Epigenetic age was associated with chronological age and VA within each group. For each group, no relevant associations of epigenetic age or age acceleration with demographic, biochemical, and clinical parameters were found. When considering individuals with PWS, there were no associations of epigenetic age with growth hormone (GH) deficiency, duration of hormone replacement therapy, and plasma levels of insulin-like growth factor 1 (IGF-1). Conclusions: The hypothesis of accelerated epigenetic ageing in PWS should be rejected. Additionally, considering the existence of a SNORD116-dependent epigenetic dysregulation in PWS, the results of the present study might be misleading, since an epigenetics-based approach was used to measure ageing.

Background: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the accumulation of fat in the liver without excessive alcohol consumption or other known liver diseases. MASLD is the most common liver disease in adolescents with obesity. The aims of this study were as follows: (i) to determine which index (waist circumference BMI, WHtR, VAI, METS-IR, METS-VF, HSI, FLI, or MetS_zscore) best explains the prevalence of MASLD in adolescents with obesity; (ii) to determine whether there was a specific index that was most strongly associated with MASLD; (iii) to assess which liver function indexes were most strongly correlated with MASLD. Methods: A total of 758 adolescents with severe obesity (BMI z-score > 2) admitted at the Division of Auxology, Istituto Auxologico Italiano, IRCCS, Piancavallo-Verbania for a 3-week multidisciplinary body weight reduction program were selected. Anthropometric parameters (stature, body mass, BMI, and waist and hip circumference) were collected, and body composition (lean and fat mass) was determined using the tetrapolar bioimpedance analysis (BIA) technique. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides (TG), and C-reactive protein (CRP) were measured using standard techniques. MASLD was diagnosed based on abdominal ultrasound results. Results: WHtR (65.76%) was the most sensitive compared with other indexes. The HSI (AUC: 0.67 (0.63–0.71, 95% CI), p-value < 0.05) showed the best performance in predicting MASLD, with the threshold for having MASLD considered at 48.22. The indexes that showed the worst performance in predicting MASLD were the MetS z-score (AUC: 0.56 (0.52–0.60)) and the VAI (AUC: 0.57 (0.52–0.61)). ALT (OR: 2.92 (2.29–3.77); 95% CI) and AST (OR: 2.52 (2.03–3.20)) were the parameters with a stronger correlation with MASLD. Conclusions: The most sensitive index for diagnosing MASLD was the WHtR, based exclusively on anthropometric parameters. HSI was the index that correlated the most with MASLD, while the parameters of liver function (ALT and AST) were the most strongly correlated with the disease and its severity.

Background/Objectives: Prader–Willi syndrome (PWS) is a rare, genetically determined neurodevelopmental disorder. Individuals with PWS face numerous challenges that significantly impact their psychological well-being and quality of life, ultimately limiting their personal and social functioning. This study aimed to evaluate the quality of life and psychological well-being in a sample of Italian adult patients with PWS compared to an age-matched control group of normal-weight Italian individuals. Methods: Thirty patients with PWS (11 men and 19 women; mean age ± SD: 36.4 ± 10.31 years; mean Body Mass Index (BMI: 35.7 ± 8.92 kg/m2) and thirty Italian adult individuals from the general population (5 men and 25 women; mean age ± SD: 32.1 ± 6.86 years; mean Body Mass Index (BMI: 21.8 ± 2.90 kg/m2) were studied. Quality of life and well-being were assessed using the Italian versions of the 36-item Health Survey Short Form and the Psychological General Well-Being Index. Results: Normal-weight subjects scored significantly higher than PWS patients on the physical health (p < 0.001) and social functioning (p = 0.047) subscales of the SF-36. Conversely, PWS patients scored higher on the vitality subscale (p < 0.001). Similarly, the vitality subscale of the PGWBI was significantly higher in PWS patients than in controls (p = 0.010), whereas the Self-Control subscale of the PGWBI was higher in controls compared to PWS patients, albeit not statistically significant (p = 0.057). Discussion: Patients with PWS exhibited impairments in various aspects of quality of life and psychological well-being, including physical, behavioral, and social domains. However, the higher vitality scores observed in PWS patients suggest a preserved dimension of their psychological well-being. Conclusions: These findings enhance the understanding of the psychological condition of patients with PWS and provide valuable insights for improving multidisciplinary psychological treatment approaches for these individuals.

Endothelial dysfunction drives obesity‐related complications. Doppler ultrasound measurement of blood flow during 1‐min passive leg movements (PLM) is a valuable non‐invasive tool for assessing endothelial function and nitric oxide (NO)‐mediated vasodilation. The objectives of this work were t o identify endothelial dysfunction biomarkers in young individuals with obesity (OB) using the PLM test; to evaluate the effects of a rehabilitation programme on these biomarkers; and to explore associations between PLM data, oxidative metabolism and blood biomarkers of microvascular impairment. Fifteen male OB (age 17 ± 4 years; body mass 121.4 ± 24.1 kg; body mass index 39.3 ± 7.5 kg m −2 ) were tested before (PRE) and after (POST) a 3‐week multidisciplinary body mass reduction programme. Fifteen age‐matched normal‐weight males (CTRL) underwent PRE measurements. Participants performed an incremental exercise, a PLM test and underwent blood biomarker analysis. Peak oxygen uptake and ventilatory thresholds (mL kg −1 min −1 ) were ∼40% lower in OB versus CTRL ( P < 0.001) and improved by ∼8% in OB POST versus PRE ( P < 0.05). Plasma nitrite concentration was lower in OB (0.18 ± 0.09 µmol L −1 ) versus CTRL (0.51 ± 0.49; P = 0.02). Baseline blood flow, normalized for appendicular muscle mass, was similar between the two groups, whereas peak blood flow, Δpeak (difference between peak and baseline) and the area under the blood flow versus time curve were significantly lower in OB PRE, with improvements in OB POST. Several blood biomarkers of endothelial barrier function and permeability differed in OB versus CTRL. The blunted PLM‐induced hyperaemic response and lower plasma nitrite levels indicate impaired endothelial function in young individuals with obesity, occurring before the onset of cardiovascular and metabolic complications.