International Journal of Obesity

Background The consequences of prolonged exposure to obesity on biomarkers of myocardial stress and injury remain unclear. We examined associations of duration and cumulative severity of obesity from childhood to later adulthood with concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), and growth differentiation factor-15 (GDF-15) at age 62 years. Methods The sample comprised 4,901 participants in the 1958 National Child Development Study who had measurements of NT-proBNP, hs-cTnI, or GDF-15 at age 62 years and at least four BMI assessments between 7 and 62 years of age. Individual BMI trajectories were modelled, from which total duration of obesity and mean excess BMI (area between the trajectory and the age-specific obesity threshold divided by duration) were derived. Associations of ever versus never having been obese, obesity duration, and mean excess BMI with biomarker concentrations were examined using general linear regression models with progressive adjustment for early-life characteristics; contemporaneous cardiometabolic factors; and health behaviours, socioeconomic position, and psychosocial factors. Nonlinear associations of obesity duration were estimated using restricted cubic splines and subsequently approximated using linear splines. Results Overall, 26.3% of participants had ever experienced obesity. There was no evidence of an association between ever versus never having been obese and NT-proBNP. Among men, ever having been obese was associated with 11.00% (95% CI, 4.62-17.37) higher hs-cTnI in the fully adjusted model, whereas there was no evidence of an association among women. Ever having been obese was associated with higher GDF-15, although the association attenuated substantially after adjustment for contemporaneous cardiometabolic factors. Longer obesity duration was associated with higher concentrations of all three biomarkers in fully adjusted models, but the pattern differed by biomarker: hs-cTnI increased approximately linearly with duration, whereas NT-proBNP and GDF-15 remained relatively stable up to approximately 25 years of obesity before increasing with longer duration. In fully adjusted models, each additional year of obesity beyond 25 years was associated with 1.80% (95% CI, 0.54-3.06) higher NT-proBNP and 0.81% (95% CI, 0.25-1.36) higher GDF-15, while each additional year across the full range of obesity duration was associated with 0.41% (95% CI, 0.07-0.76) higher hs-cTnI. Among participants who had ever experienced obesity, each 1 kg/m2 higher mean excess BMI was associated with 4.02% (95% CI, 1.79-6.24) higher NT-proBNP and 2.00% (95% CI, 0.49-3.51) higher hs-cTnI in fully adjusted models; there was no evidence of an association with GDF-15. Conclusions Longer duration of obesity was associated with higher concentrations of biomarkers reflecting myocardial stress, injury, and cellular stress at age 62 years, with associations particularly evident after approximately 25 years of obesity for NT-proBNP and GDF-15. These findings suggest that duration of obesity may provide clinically relevant information beyond current obesity status, supporting its consideration as an additional dimension of cumulative obesity burden in cardiovascular risk assessment.

Background: Early postoperative weight loss may help predict later outcomes, but its reliability for longer-term weight loss and regain remains unclear. We assessed whether the percentage total weight loss (%TWL) 3 months after metabolic/bariatric surgery predicted later %TWL weight change/regain. Methods: This retrospective observational cohort study included 216 patients from a prospectively pre-recruited multicentre bariatric surgery cohort who underwent sleeve gastrectomy or Roux-en-Y gastric bypass and had 3-month %TWL and at least one later outcome. Linear regression assessed associations between 3-month %TWL and later %TWL plus weight change/regain outcomes. Adjusted incremental R2 quantified the additional variance explained by 3-month %TWL. Secondary procedure-stratified, diabetes-stratified, and baseline BMI comparator analyses are reported in the Supplementary Material. Results: Greater 3-month %TWL was associated with higher 1-year and 2-year %TWL in adjusted models (both p < 0.001) but not longer-term %TWL (p = 0.078). Incremental R2 was 38.23% for 1-year, 11.75% for 2-year %TWL and 2.25% for long-term %TWL. Greater 3-month %TWL was also associated with greater recurrent weight gain from 1 to 2 years and from 1 year to long-term follow-up. In secondary analyses, findings were broadly consistent across procedure and diabetes subgroups, while 3-month %TWL explained more additional variance in 1-year %TWL than baseline BMI Conclusion: 3-month %TWL predicted 1-year and 2-year outcomes but not longer-term %TWL, supporting its value as an early marker of postoperative weight trajectory. Heterogeneity in recurrent weight stability may contribute to weaker long-term prediction and warrants further study to determine whether early weight-loss patterns can identify patients requiring closer long-term weight management support.

Purpose: In high-income countries, lower socioeconomic position (SEP) is linked to higher childhood obesity prevalence but its association with cardiometabolic risk in those presenting in pediatric weight management services remain underexplored. Methods: In the Bern Obesity in Childhood and Adolescence Biorepository (BOCAB), we used the Swiss neighborhood index of SEP (0-100, 100=highest SEP) to assess cross-sectional associations with obesity severity and cardiometabolic risk factors, mediation by behavioral lifestyle factors and longitudinal associations between SEP and percentage of the 95th BMI percentile (%BMIp95) and waist circumference-to-height ratio (WHtR), adjusted for age and sex. Results: Among 886 participants (52% male, mean age 11.2 years [SD 3.1]), mean %BMIp95 was 124% (SD 17%). A 10-unit higher SEP was associated with lower %BMIp95 ({beta} -2.57; 95% CI -3.84 to -1.31) and lower WHtR ({beta} -0.006; -0.010 to -0.001), both partially mediated by weekly physical activity and screen time. Higher SEP was also associated with lower odds of insulin resistance (OR 0.80; 0.65 to 0.98), low HDL-cholesterol (OR 0.81; 0.67 to 0.98), elevated non-HDL-cholesterol (OR 0.74; 0.59 to 0.92) and elevated triglycerides (OR 0.83; 0.70 to 0.98). Among 419 participants with longitudinal data, annual reduction in %BMIp95 and WHtR did not differ by SEP. Conclusion: Lower SEP is associated with greater obesity severity and cardiometabolic risk among children and adolescents with obesity presenting at specialized tertiary care. Screening and early referral of lower-SEP children and adolescents with obesity should be encouraged, before cardiometabolic risk accumulates, particularly since treatment response did not differ once enrolled.

Background: Both fetal and maternal genomes contribute to birthweight, but the timing and relative magnitude of their effects during gestation remain unclear. Polygenic risk scores (PRSs), constructed from genome-wide association studies (GWAS), capture the cumulative influence of common birthweight-associated variants to quantify genetic predisposition to fetal growth. We constructed fetal and maternal PRSs for birthweight in two UK birth cohorts, the Pregnancy Outcome Prediction Study (POPS) and Born in Bradford (BiB), to evaluate their associations with estimated fetal weight (EFW) throughout pregnancy and with birthweight at delivery. We also investigated whether PRSs could improve risk stratification of infants born below the 10th centile by distinguishing those with pathological intrauterine growth restriction (IUGR) from those who are constitutionally small-for-gestational-age (SGA). Methods: In POPS and BiB, we used LDpred2-auto to estimate PRSs based on the largest available maternal and fetal GWAS for birthweight. We longitudinally assessed EFW associations with PRSs using linear mixed effects models in POPS and BiB. We evaluated birthweight associations with PRSs using linear models, where birthweight was adjusted for gestational age and fetal sex. We estimated R2 and conducted variance decomposition analyses for all models. Genetically-predicted birthweights were estimated from joint models of fetal and maternal PRSs plus ten genetic principal components (PCs). BiB analyses were conducted separately for genetically-inferred European (EUR) and South Asian (SAS) ancestry. Results: While PRSfetus was significantly associated with EFW at baseline ([~]22 weeks gestation) across cohorts, PRSmother was not. Both the interaction of PRSfetus and PRSmother with gestational age (GA) were significantly associated with EFW. The effect of PRSmother on EFW increased more quickly across gestation than the effect of PRSfetus in POPS, but this finding was not replicated in BiB. Jointly, fetal and maternal polygenic risk explained 4% of variance in EFW in POPS and 1% in BiB-EUR. In POPS, fetal and maternal PRSs showed independent contributions to EFW variance of 3% and 0.5%, respectively. Joint and univariable linear models showed significant positive associations of PRSfetus and PRSmother with observed birthweight. In POPS, PRSfetus and PRSmother accounted for [~]10% and [~]4% of variance in birthweight over covariates alone, respectively, which was replicated in BiB-EUR. Maternal and fetal genetic effects jointly explained 11% of birthweight variance in POPS, similar to BiB-EUR, at 12%; however, the variance explained was reduced by half in BiB-SAS, at 6%. Among POPS babies born <10th birthweight centile, the magnitude of the difference between observed and genetically-predicted birthweight was greater in the group judged clinically to be IUGR vs. SGA (p=0.008; point estimate=0.29, 95%CI: 0.12, 0.47). Conclusions: Maternal and fetal PRSs jointly account for [~]11-12% of birthweight variance in European ancestry groups, but much less in a South Asian cohort. In POPS, the effect of birthweight-associated SNPs on estimated fetal weight increases more rapidly across pregnancy for maternal than for fetal genetic effects. Deviation from genetically-predicted birthweight may be a useful metric to help distinguish growth-restricted from constitutionally small babies.

Background: Incretin-based obesity medications (IOMs) produce substantial weight loss, but the incremental benefit of structured nutritional therapy when integrated with pharmacotherapy remains unclear. Objectives: To compare 12-month weight-loss outcomes between individualized carbohydrate-reduced nutritional therapy combined with IOMs (VINT+IOM) and IOM-based care without structured nutritional therapy (IOM only). Methods: This retrospective cohort study evaluated 4,269 adults enrolled in a comprehensive telemedicine obesity care program (VINT+IOM, n=1,658; IOM only, n=2,611). Both pathways included clinician-guided medication management and behavioral coaching. The primary analysis focused on GLP-1-naive participants receiving either semaglutide or tirzepatide without switching medications during follow-up. Adjusted weight changes were estimated using longitudinal linear mixed-effects models accounting for baseline demographic and clinical characteristics. Additional analyses evaluated weight-loss responders, prior GLP-1 exposure, and medication utilization. Results: Among GLP-1-naive semaglutide users, adjusted 12-month weight loss was greater with VINT+IOM than IOM only (30.7 vs. 24.1 lb; P=0.01), with corresponding observed weight loss of 13.3% versus 11.1%. Among tirzepatide users, adjusted weight loss was 45.9 versus 34.4 lb (P=0.003), with observed reductions of 19.7% versus 15.6%, respectively. Weight-loss responder rates consistently favored VINT+IOM. In the overall cohort, including GLP-1-naive participants, those with prior GLP-1 exposure, and participants with varying medication trajectories, adjusted weight loss was 29.4 versus 21.5 lb (P less than 0.001), with observed reductions of 12.7% versus 9.6%. Greater weight loss with VINT+IOM was also observed among participants with prior GLP-1 exposure. Weight loss continued between 6 and 12 months in both pathways. Medication coverage was high, with approximately 80% of participants achieving a proportion of days covered of at least 80% in both pathways. Conclusions: Integrating individualized carbohydrate-reduced nutritional therapy with IOM-based care was associated with greater 12-month weight loss than IOM-based care without structured nutritional therapy. These real-world findings support further evaluation of individualized nutritional approaches as an adjunct to incretin-based obesity pharmacotherapy.

Background & Aims: Childhood obesity is a complex, heterogeneous disease. Children with obesity are often grouped into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) phenotypes, although this classification may oversimplify the underlying metabolic diversity. We aimed to characterise the metabolic profiles associated with the conventional MHO/MUO classification and to identify data-driven metabolic profiles in 267 children and adolescents with obesity. Methods: In this cross-sectional study, we used serum 1H-NMR spectroscopy to quantify lipoproteins, glycoproteins, low-molecular-weight metabolites, and lipid fractions. Univariate comparisons and partial least squares discriminant analysis (PLS-DA) were used to characterise NMR-derived variables associated with MHO and MUO groups. We applied unsupervised k-means clustering based on principal component scores to identify data-driven metabolic profiles independent of the predefined clinical phenotypes. Results: Forty-one NMR-derived variables differed between MUO and MHO (FDR q-value < 0.05), predominantly in the triglyceride-rich lipoprotein and glycoprotein profiles, of which 31 were elevated in MUO. PLS-DA discriminated between MHO and MUO (AUC = 0.84, Q2 = 0.33; permutation p < 0.001). Unsupervised clustering identified two data-driven metabotypes that only partially overlapped with the clinical phenotypes: 27% of children with MHO clustered within the adverse metabolic profile (Cluster 2), characterised by a triglyceride-rich and inflammation-associated profile, whereas 41% of children with MUO were assigned to the comparatively favourable profile (Cluster 1). Clustering further revealed additional differences in lipoprotein subclasses and lipid composition that the MHO/MUO classification did not capture. Conclusions: The conventional MHO/MUO classification captures an important component of metabolic variation in childhood obesity but does not fully capture cardiometabolic heterogeneity. Quantitative 1H-NMR metabolomics identified putative metabotypes characterised by differences in lipoprotein composition and cholesterol distribution beyond clinical phenotypes. These findings support the potential value of metabolomic profiling to refine cardiometabolic risk stratification in children with obesity; however, the relevance of these data-driven metabotypes requires confirmation in independent cohorts and longitudinal follow-up studies.

Background: Handgrip strength is associated with cardiometabolic abnormalities, but whether it adds information once detailed adiposity and muscle mass are known is unclear. Methods: We studied adults aged 40-59 years from NHANES 2011-2012 (development, n=508) and 2013-2014 (temporal validation, n=616). The outcome was at least two of four non-adiposity abnormalities (elevated blood pressure, fasting glucose or triglycerides, or low HDL cholesterol); waist circumference was not part of the outcome. A prespecified feature ladder added DXA body fat percentage and visceral adipose tissue to age, sex, BMI and waist circumference (M1), then appendicular skeletal muscle index (M2), then absolute (M3A, primary) or weight-normalised (M3B) grip strength. Logistic regression was primary; elastic-net and XGBoost were supportive. Development performance used nested cross-validation; frozen models were scored once in the validation cohort. Paired increments used 2000 stratified bootstrap resamples. Results: The outcome occurred in 249 (49.0%) and 277 (45.0%) participants. Adding adiposity increased the logistic regression AUC by 0.0209 (95% CI 0.0024-0.0402) in development and 0.0209 (0.0032-0.0375) in temporal validation. Adding absolute grip strength to M2 changed the AUC by -0.0046 (-0.0107 to 0.0013) and 0.0045 (-0.0009 to 0.0098), respectively. All 12 grip-strength AUC increments across algorithms, definitions and cohorts had intervals that included zero. Calibration was unchanged and the incremental net benefit was not consistently positive. Model attributions to grip strength varied by algorithm. Conclusions: In middle-aged adults, detailed adiposity, but not grip strength, added reproducible information for concurrent cardiometabolic risk stratification beyond conventional anthropometry and muscle mass.

Enhanced excitability of output neurons in the olfactory bulb (OB) has been linked to regulation of energy homeostasis. The mechanism by which the olfactory system can drive metabolic state while processing odor information remains elusive yet must depend upon integration and relay to the rest of the brain. Herein, we screened brain-wide neuronal ensembles that preferentially engaged during odor stimulation (referred to as ODORTRAP) utilizing FOSTRAP activity mapping. Mice were exposed to the odor isopropyl tiglate (IPT), a preferred ligand for the olfactory receptor 160, previously shown to be vulnerable to diet-induced obesity. Odor activation resulted in elevated labelling in the olfactory bulb (ODORTRAP) (p < 0.001), as well as in higher olfactory cortices including anterior olfactory nucleus, piriform cortex, and cortical amygdala (p < 0.05). Interestingly, IPT differentially recruited hypothalamic feeding areas, namely the arcuate (ARC), dorsomedial (DMH) and lateral (LH) hypothalamus (p < 0.001), while the ventromedial hypothalamic nucleus and the suprachiasmatic nucleus exhibited no change in ODORTRAP activity (p > 0.05). In mice that were maintained on moderately high-fat (MHF) diets, we discovered that obesity re-models the activation pattern across the brain. Obese mice exhibited loss of ODORTRAP activity in the ARC (p < 0.0001), whereas in the DMH and LH increased baseline activity that obscured any odor-linked neural activity. While IPT activated the nucleus accumbens and medial septum in control mice (p < 0.01), obese mice demonstrated no changes in ODORTRAP activity (p > 0.05). Our study identifies key brain regions linking chemosensation and metabolic state, specifically demonstrating alteration in activity in hypothalamic domains upon obesogenic diet.

Adult obesity, including morbid obesity, has reached epidemic proportions worldwide. Yet, the current genetic models based on BMI-associated common variants identified through genome-wide association studies (GWAS) explain only a modest fraction of BMI variability. Contribution of rare and low-frequency variants to polygenic obesity remains incompletely defined. Leveraging whole-exome sequences of 1138 adults spanning normal-weight, overweight, obese and morbidly obese (MO) categories from Kuwait and Qatar, we catalogued cohort-specific rare and low-frequency deleterious variants differentiating MO individuals from normal-weight individuals. Cross-cohort comparisons identified 147 risk variants seen in [&ge;]2 MO individuals from one cohort and in [&ge;]1 MO individual from the other; among these, 27 variants occurred in [&ge;]2 MO individuals from each cohort. The risk genes were enriched in obesity-related pathways and tissues, with most harbouring GWAS variants associated primarily with obesity traits followed by metabolic and brain-related traits. Duodenal tissue expression data exhibited significant dysregulation of key risk genes in MO individuals. Variants from the 147-list and 27-list occurred in 87% and 49% of MO individuals, respectively; MO-variant burden correlated positively with BMI (r=0.30 and r=0.31, respectively) across the overweight-obese-MO categories. Combinations of a finite set of low-frequency coding variants substantially shape the continuum of polygenic obesity.

Importance: Pediatric obesity affects 1 in 5 US children and has been linked to brain structural differences. Most evidence is cross-sectional and models body mass index (BMI) linearly, with metrics that compress severe obesity. Objective: To examine associations between brain structure and BMI for age across the weight spectrum and Centers for Disease Control and Prevention (CDC) weight status categories, distinguishing between and within person associations, and their age and sex moderation. Design, Setting, and Participants: Longitudinal cohort study of youth aged 8 to 10 years at baseline in the US community based Adolescent Brain Cognitive Development Study (4 waves, 2016 to 2025; ages 8 to 18 years). Exposures: Extended CDC BMI-for-age z-score, grouped by wave-mean z-score: underweight (<5th percentile, n=297), healthy weight (5th to <85th, n=7,452), overweight (85th to <95th, n=1,919), and obesity ([&ge;]95th, n=1,842). Main Outcomes and Measures: Cortical thickness (12 regions) and subcortical volume (7 regions) from T1 weighted magnetic resonance imaging (MRI), defined a priori. Results: Among 11,510 participants contributing 32,212 observations (mean [SD] age, 12.6 [2.5] years; 52.2% male), higher between person BMI for age z was associated with lower frontal and temporal thickness (6 regions) and larger subcortical volume (5 regions; all q < .001), but associations were nonlinear (17 of 19 regions). Youth with obesity had lower thickness than healthy weight youth in 8 frontal and temporal regions (largest, -0.21 SD; q < .001), with dorsal frontal differences decreasing across adolescence; underweight youth had smaller subcortical volumes. Higher BMI for age z was associated with larger subcortical volume (all 7 regions) within the healthy weight category and lower cortical thickness (11 of 12 regions; fusiform: {beta} = -0.27; q < .001) within the obesity category, steeper than in healthy weight youth in 10 regions, but not in overweight or underweight youth. Within person associations did not reproduce the obesity associations, reversed from negative at age 10 to positive at age 16, and were more negative in female than male participants. Conclusions and Relevance: Youth with obesity had lower cortical thickness than healthy weight peers, but associations between brain structure and BMI for age differed between CDC weight status groups, suggesting a complex relationship between adiposity and brain structure.

Background: Added sugars during early development may influence adiposity, but whether associations vary by developmental timing and child sex is unclear. Objectives: To determine whether child sex modifies associations of added sugars and fructose exposure from pregnancy through 24 months with body composition at 24 months. Methods: This secondary longitudinal analysis included 130 mother-child dyads. Maternal diet was assessed during mid-pregnancy and child diet at 2wk and 6mo (infancy), and 12mo and 24mo (toddlerhood). Multivariable regression tested sex-by-exposure interactions for anthropometric outcomes; 42 children had usable dual-energy X-ray absorptiometry (DXA) data. Results: Prenatal added sugars were more positively associated with percentage body fat and total and regional fat mass in girls than in boys. Prenatal fructose was more positively associated with waist circumference in boys. During infancy, added sugars were more positively associated with percentage body fat and total and regional fat mass in boys, whereas fructose was more positively associated with fat-free mass in girls. Conclusions: Associations of early-life sugars exposure with body composition varied by developmental timing and child sex. Findings from the smaller DXA subset are exploratory and require replication but suggest that susceptibility to early dietary sugars may differ across developmental windows.

Objective: Overweight and obesity in childhood and adolescence are major risk factors for health problems across the lifespan. This manuscript reports the current prevalence of overweight and obesity among children and adolescents aged 4-17years living in Germany and compares them with previous population-based results. Methods: A representative, cross-sectional sample of 4-17-year-olds was drawn following a multistage sampling process. Analyses are based on weight and height of 3,978 individuals measured in the field by trained test instructors between 2023-2025. Overweight and obesity classification was defined using age- and sex-specific body-mass-index percentiles. To allow for comparability of prevalence estimates derived from previous assessment waves and other panel studies dating back to 2005, an alignment factor was derived using an inverse probability of participation weighting approach. Together with sampling weights, the alignment factor was applied to obtain current, representative prevalence estimates of overweight and obesity. Results: The aligned, weighted prevalence of overweight and obesity was 16.1% (95%CI[14.5-17.9%]), whereas prevalence of obesity was 6.7% (95%CI [5.5-8.1%]). Age- and sex-specific prevalence rates are reported and compared to previous waves. Conclusions: The current prevalence of overweight and obesity in children and adolescents aged 4-17 years living in Germany remains stable over the past two decades.

The extracellular matrix (ECM) of adipose tissue regulates metabolic homeostasis, yet how ECM composition drives adipose dysfunction in obesity remains only partially defined. Multi-omics profiling of visceral adipose tissue identified the multidomain ECM protein SVEP1 as a candidate regulator of adipose remodeling; SVEP1 was elevated in obese human adipose tissue and correlated with insulin resistance and systemic inflammation, and interaction analysis predicted associations with ECM proteins, integrins, and cytoskeletal regulators. On a chow diet, Svep1 heterozygous (Svep1+/-) mice gained less weight with lower fasting glucose, and their adipocytes showed enhanced lipolysis and AMPK activation. On a high-fat diet, Svep1+/- mice exhibited attenuated adiposity, improved glucose tolerance and insulin sensitivity, and fewer adipose macrophages with a shift away from a pro-inflammatory profile, alongside downregulation of inflammatory, lipid-metabolic, and ECM-remodeling pathways. Decellularized Svep1+/- matrix altered macrophage adhesion and phenotype relative to Svep1+/+ matrix, identifying SVEP1 as a matrix-borne mediator coupling adipose remodeling to immune activation and metabolic impairment. Together, these findings position the adipose ECM as an active driver of immunometabolic dysfunction and nominate SVEP1 and its receptor network as candidate targets in obesity.

The post-ingestive dopamine response is an integral determinant of subsequent eating behavior in animals yet measurement of the post-ingestive response to nutrients in humans has been elusive when assessed in the early post-ingestive period (30 minutes postprandially). We conducted secondary analysis comparing dopamine D2 receptor binding potential (D2BP) measured using [18F]fallypride positron emission tomography in two inpatient controlled feeding cohorts consuming standardized diet (50% carbohydrate; 35% fat; 15% protein) with similar characteristics and procedures but differing in time since last meal: confirmed overnight fast (n=57; 66.7% female; BMI 29.6{+/-}7.6 kg/m2; 31.9{+/-}7.2 years old) and 2-hours after a standardized meal reflecting 20% of energy requirements (n=43; 48.8% female; BMI 28.8{+/-}7.8 kg/m2, 31.3{+/-}7.7 years old). Compared to the fasted cohort, the 2-hour postprandial cohort exhibited significantly reduced whole striatal D2BP (p<0.0001) as well as in clusters in insular cortex, prefrontal cortex which remained after adjustment for age, sex, and insulin sensitivity. Voxelwise comparisons of the relationship between D2BP and BMI in the fasted and fed cohorts reveals clusters within dorsolateral and ventral striatum where dopamine level is dependent on postprandial state and adiposity. Given the similarities between protocol procedures and participant characteristics, our results suggest that the post-ingestive dopamine response to nutrients may be prominent in the extended post-ingestive period and warrant investigation within-subject.

Background: Intramuscular fat and fibrous tissue deposition increase with ageing, disuse, and disease and contribute to impaired muscle function and reduced 'muscle quality'. Magnetic resonance imaging (MRI) and biopsy provide reference measures of muscle composition, but their cost, invasiveness, and limited accessibility restrict routine use. B-mode ultrasonography has emerged as a practical, low-cost alternative, with ultrasound-derived echo intensity widely interpreted as a surrogate measure (index) of intramuscular fat, fibrosis, and 'muscle quality'. However, such interpretation warrants further scrutiny. Aim: To quantify the relationship between ultrasound-derived echo intensity and reference measures of intramuscular fat and fibrous tissue and determine whether these relationships vary across muscles or according to anatomical and methodological factors. Methods: A systematic search of six databases was conducted (last search: August 2026). Human and animal studies reporting correlations between echo intensity and measures of intramuscular fat or fibrous tissue using MRI, histology, or chemical analysis were synthesised using multilevel random-effects meta-analysis with study-level cluster-robust inference. Correlations were Fisher z-transformed and back-transformed for interpretation. Exploratory analyses examined fat compartment, muscle, muscle architecture, health status, study model, and distance-correction procedures. Results: Twenty-eight studies met the eligibility criteria. For intramuscular fat, 204 effects from 23 independent studies yielded a weak-to-moderate pooled correlation with echo intensity (r=0.54, 95% CI: 0.45-0.61; 95% PI: - 0.02-0.84; P<0.01), with substantial heterogeneity (I^2=74.5%). The wide prediction interval suggests the true correlation could range from negligible to strong. No significant moderation effects were observed for study model (animal vs. human: r=0.46 vs. 0.55; P=0.26), health status (clinical vs. healthy: r=0.64 vs. 0.49; P=0.11), probe-to-muscle distance correction (corrected vs. raw echo intensity: r=0.57 vs. 0.53; P=0.25), or muscle architecture (non-pennate vs. pennate: r=0.63 vs. 0.53; P=0.56), although some categories contained few studies and effects. Model-based inference indicated significant moderation effect of lipid compartment (intramyocellular lipid vs. total intramuscular fat vs. extramyocellular lipid: r=0.10 vs. 0.57 vs. 0.49; P<0.001) but this effect was not significant under cluster-robust inference (P=0.50). For fibrous tissue, six effects from four studies yielded a weak, non-significant pooled correlation (r=0.34, 95% CI -0.39, 0.81], 95% PI [-0.85, 0.96]; P=0.24). Conclusions: Echo intensity is weakly-to-moderately associated with intramuscular fat, and this varied substantially across studies and muscles, whereas evidence for intramuscular fibrous tissue is limited and uncertain. These findings provide limited support for interpreting echo intensity as a surrogate measure or an index of intramuscular fat or fibrosis or, on this basis, as an index of 'muscle quality'.

Background: University life can influence food choice even among physically active students. This study examined nutritional awareness, emotional, external, and restrained eating, body mass index (BMI), and estimated resting metabolic rate (RMR) in physical education students, and assessed differences by sex and academic level. Methods: A descriptive, analytical and correlational design was used. The sample included 160 physical education students (95 women and 65 men; mean age 20.42 {+/-} 1.53 years) from An-Najah National University. Nutritional awareness was assessed with a 15-item scale, and eating behaviour with the 33-item Dutch Eating Behavior Questionnaire. BMI was calculated from measured height and body mass, and RMR was estimated using an equation developed for athletes. Correlations, group comparisons, robust interaction models, and hierarchical regression were applied. Results: Nutritional awareness was high (3.73 {+/-} 0.81), whereas emotional (3.11 {+/-} 1.18), external (3.20 {+/-} 0.95), and restrained eating (3.25 {+/-} 1.11) were moderate. Higher awareness was associated with less emotional (r = -0.617) and external eating (r = -0.652), but greater restrained eating (r = 0.644; all q < 0.001). These associations remained after adjustment. Men reported more external eating, while women reported more restrained eating. Eating patterns also varied by academic level. BMI and estimated RMR showed weaker and less consistent associations with eating behaviour. Conclusions: Nutritional awareness was closely associated with reported eating behaviour, whereas BMI and estimated RMR were less informative. Sex and academic-level differences suggest that nutrition education for physical education students may be more useful when adapted to specific behavioural patterns. The findings represent associations and group differences and do not establish causal relationships. Keywords: physical education students; nutritional awareness; eating behaviour; emotional eating; external eating; restrained eating; body mass index; resting metabolic rate

Postmenopausal women are vulnerable to metabolic dysfunction. Compelling evidence suggests this is because they lack the protective effects of estrogens. We have shown that circulating estrogens regulate daily eating and activity rhythms in female mice and protect them from obesity and metabolic dysfunction. However, few studies have investigated whether postmenopausal women have disrupted eating and sleep-activity rhythms that could contribute to metabolic dysfunction. The purpose of this cross-sectional study was to investigate the relationship between sleep and eating rhythms and metabolic risk in postmenopausal women with overweight or obesity. Seven days of sleep and food intake behavior data were collected from postmenopausal women with overweight or obesity. Sleep timing was assessed using wrist-worn actigraphy and sleep logs. First and last calorie intake times were collected daily using text messaging. Visceral adipose tissue (DXA), insulin resistance (Matsuda index), blood pressure, and triglycerides were analyzed as markers of metabolic risk. In 122 postmenopausal women (mean {+/-} SD: 58.1 {+/-} 3.6 yr, 33.2 {+/-} 5.2 kg/m2 BMI), we found that later sleep onset was associated with greater visceral adipose tissue (p=0.0007), but not insulin resistance, blood pressure, or triglycerides. Next, we used a random forest model to quantify the relative contributions of sleep and meal timing variables to predict visceral adipose tissue. The top predictors of visceral adipose tissue were time of sleep onset, sleep duration, and time of last caloric intake. These data suggest that interventions that advance sleep onset may reduce metabolic risk in postmenopausal women.

Background: Whether whole-body energy balance is associated with perceived stress in young adults is unclear. Aim: To examine associations of estimated free-living energy balance with physical and psychological stress during 28-day monitoring. Methods: This secondary analysis of an observational study included 18 Japanese male university students with at least 14 valid accelerometer days (at least 600 min/day). Energy intake was estimated using the Brief-type Self-administered Diet History Questionnaire; total energy expenditure was estimated from accelerometry plus resting metabolic rate. Physical and psychological stress were assessed before and after monitoring using 100-mm visual analog scales. Baseline-adjusted linear regression was used. Summary: Mean energy balance was -79 kcal/day (SD 531). Energy balance was not clearly associated with post-monitoring physical stress (B = 0.067 per 100 kcal/day, 95% CI -1.604 to 1.737; p = 0.933) or psychological stress (B = 0.314, 95% CI -2.571 to 3.199; p = 0.820). No clear association between estimated free-living energy balance and post-monitoring stress was detected.

Background: Thinness-oriented body ideals are well described among young Japanese women, but variation in visual and numerical ideals by sex, age, and current BMI remains unclear. Methods: We analysed an unweighted web-panel sample of 27,359 Japanese adolescents and adults aged 15-69 years from the Survey of Body Shape and Health Awareness in Japanese People, a cross-sectional web-based survey. Current and ideal BMI were derived from self-reported height and weight, and visual orientation from ideal versus perceived current silhouette. Adult BMI-stratified analyses included participants aged 20-69 years. Findings: Among 27,359 participants (10,094 men and 17,265 women), relative thinness-oriented indicators increased with current BMI in both sexes. Among normal-weight women, 74.7-83.7% selected a smaller ideal silhouette and 79.2-91.2% reported an ideal BMI lower than current BMI. These indicators were also present among underweight women aged 20-29 years (44.9% and 43.4%, respectively), but declined with age. Most underweight men reported weight-gain-oriented ideals. Fine stratification showed that thinness-oriented ideals among women were common in low-normal and mid-normal BMI strata. Interpretation: Body-size ideals differed by sex, age, and current BMI. Thinness-oriented ideals among women extended beyond obesity and young adulthood, whereas underweight men generally preferred a larger body. Longitudinal and behavioural studies are needed. Funding: Cabinet Office of Japan Strategic Innovation Promotion Program (SIP), "Inclusive Community Platform" (grant no. SIPCP23C02).

Abstract Background: Randomized trials show substantial weight loss with semaglutide and tirzepatide under structured care, but little is known about whether patients in routine practice continue therapy, reach a maintenance dose, and have their weight measured. Objectives: To describe the first year after initiation of semaglutide or tirzepatide for obesity, including care patterns, maintenance-dose attainment, weight documentation, and total body weight loss (TBWL). Methods: This retrospective cohort study used Epic Cosmos, an electronic health record network of >350 US health systems, to identify adults with obesity and without diabetes who initiated injectable semaglutide or tirzepatide in 2024. Outcomes over 12 months included prescribing persistence, discontinuation, switching, add-on therapy, and reinitiation; attainment of Food and Drug Administration (FDA)-labeled maintenance doses; availability of follow-up weight; and TBWL across progressively restricted populations. Results: Among 743,153 adults (60.1% semaglutide; mean age, 48.5 years; 72.5% female), 12-month prescribing persistence was 29.9% for semaglutide and 35.9% for tirzepatide. FDA-labeled maintenance-dose attainment was 28.3% and 55.0%, respectively, and only 8.8% and 16.4% remained prescribing persistent at a maintenance dose with a recorded weight at 12 months. About half of initiators lacked a 12-month weight. Among all initiators, [&ge;]5% TBWL was documented in 25.6% (semaglutide) and 30.4% (tirzepatide), rising to 51.9% and 61.9% among those with recorded weight, 66.1% and 79.5% among those also prescribing persistent, and 82.9% and 87.3% among those further at a maintenance dose. Conclusions: In routine practice, most patients initiating semaglutide or tirzepatide did not remain on therapy, reach a maintenance dose, and have weight documented through the first year. Documented weight loss was greatest among those completing each step of care, suggesting continuation, dose escalation, and monitoring as targets for improvement.