Obesity

Current recommendations suggest that women achieve a healthy weight before becoming pregnant, but evidence supporting the benefits of preconception weight loss are limited and inconsistent, with some evidence of risks. The Maternal Preconception Weight Trajectory (MatTrack) study will evaluate the impact of preconception weight change on maternal, pregnancy, and child outcomes. In this paper, we present methods used to construct the cohort and evaluate baseline characteristics. The MatTrack cohort was derived from electronic health record data from four Kaiser Permanente regions. Inclusion criteria addressed data quality, availability, and enrollment; maternal age ([≥]18 years); and date (pregnancy onset date in 2006-2020, delivery [≤]12/31/2020). Starting body mass index (BMI) was calculated using weight closest to 24 months prior to pregnancy onset date and adult height. Preconception weight change rates from 24 months prior to and through pregnancy onset date were estimated using linear mixed effects models. Descriptive analyses characterized the baseline characteristics of the cohort. The cohort includes 297,592 pregnancies with the full spectrum of starting BMI: underweight (2.3%), normal weight (41.8%), overweight (28.4%); and obesity class I (15.3%), II (7.4%), and III (5.0%). The cohort is demographically diverse, with 8.3% covered by Medicaid; and 44.5%, 9.2%, and 10.9% Hispanic, non-Hispanic Black, or non-Hispanic Asian, respectively. Preconception weight change rates (kg/year) span weight loss to gain, with the greatest loss in those with obesity class III [median (10th, 90th percentile): -0.8 (-9.5, 4.9)] and the greatest gain in those with underweight [median (10th, 90th percentile): 1.1 (-0.7, 3.6)]. Longitudinal data from this cohort of nearly 300,000 linked maternal-child dyads will enable examination of associations between preconception weight loss and pregnancy, maternal, and child health outcomes. Findings will strengthen the evidence base for preconception weight management guidelines.

Background Lifestyle interventions are central to obesity prevention and management, yet interindividual variability in response remains incompletely understood. Here, we leveraged genetically defined, distinct obesity endotypes to examine lifestyle-body mass index (BMI) associations across biological pathways. Methods In the UK Biobank, we analyzed 305,713 participants with partitioned polygenic scores (pPSs) representing 10 obesity endotypes. We evaluated interactions between endotype-specific genetic susceptibility and physical activity, diet, sedentary behavior, and sleep on BMI using multivariable linear regression. Primary findings were externally evaluated in the All of Us Research Program using Fitbit-derived lifestyle measures. Results Favorable lifestyle behaviors were associated with lower BMI for all obesity endotypes, but the magnitude of these associations varied significantly across endotypes. Higher endotype-specific pPSs strengthened the benefits of physical activity (7 endotypes), healthy diet (3 endotypes), nonsedentary behavior (5 endotypes), and adequate sleep (7 endotypes) on BMI. Distinct endotypes demonstrated the greatest responsiveness to different lifestyle domains, with the metabolically unhealthy endotype showing the strongest interaction with physical activity, metabolically healthy endotype with sedentary behavior, hypothalamic dysregulation endotype with diet, and hypoinsulin 2 endotype with sleep, corresponding to differences in BMI of 0.22-0.49 kg/m2 between the highest and lowest pPS deciles. These interaction patterns were consistent in the All of Us cohort. Conclusions Obesity endotypes modify the association between lifestyle behaviors and BMI, demonstrating that responsiveness to lifestyle behaviors is heterogeneous and pathway dependent. These findings provide a framework for precision obesity prevention by identifying individuals who may derive greater benefit from specific lifestyle interventions.

Background: Heat-inactivated postbiotics derived from Lactiplantibacillus plantarum have been proposed to support weight management and metabolic health by acting on the gut-metabolic axis, including endogenous glucagon-like peptide-1 (GLP-1) signaling. resM is an orally delivered formulation combining heat-inactivated L. plantarum RSB11 (RSB11-HI) with vitamin D3, vitamin B12, chromium picolinate, white mulberry (Morus alba) leaf, and fenugreek (Trigonella foenum-graecum) seed extracts. We tested the effects of resM on body weight and a panel of metabolic outcomes in adults with overweight or obesity. Methods: In a randomized, double-blind, placebo-controlled, parallel-group trial (NCT06911073), 80 adults with overweight or obesity were allocated 1:1 to oral resM or matched placebo for 8 weeks. The trial was conducted in a fully remote, direct-to-consumer setting. The primary outcome was absolute change in body weight at the final scheduled weekly assessment, Week 7, corresponding to completion of the 8-week intervention. Secondary outcomes included body-mass index; fasting insulin, HbA1c, and HOMA-IR; serum active GLP-1; strain-specific stool quantitative PCR for L. plantarum RSB11; food cravings measured using the Food Craving Questionnaire-Trait-reduced; depressive symptoms measured using the PHQ-9; safety laboratory measures; and adverse-event surveillance. Between-group differences were evaluated using independent-samples t-tests and baseline-adjusted ANCOVA, and within-group changes were evaluated using paired tests. Results: Body weight decreased by 2.6 kg, or 3.0%, in the resM group and increased by 0.5 kg, or 0.6%, in the placebo group. Food-craving scores fell by 15.1 points within the resM arm during the 8-week intervention (p<0.001), as did depression scores. Active GLP-1 approximately doubled among participants treated with resM and increased more than in the placebo group. Serum GLP-1 levels correlated with L. plantarum RSB11 levels in stool samples in the resM arm. Safety laboratory values remained within reference ranges, gastrointestinal symptoms were reported more frequently with placebo than with resM, and no serious adverse events were reported in either group. Conclusions: Over 8 weeks, resM produced clinically meaningful weight loss within the intervention group and compared with placebo, together with reductions in food cravings and depression scores and an approximately two-fold increase in active GLP-1. Larger and longer-duration trials are needed to confirm the persistence and generalizability of these findings.

Purpose: Nighttime fasting intervals (NFIs; i.e., the longest period between the last eating episode of the day and the first of the next day) are associated with depressive symptoms in non-pregnant populations. However, this chrono-nutrition indicator has rarely been explored in the perinatal period, when individuals experience dramatic physiological and psychological changes. We explored potential associations between NFIs and depressive symptoms during the perinatal period. Methods: This secondary analysis included 232 individuals with pre-pregnancy body mass index (BMI) [&ge;]25 kg/m2. Participants were assessed during early-pregnancy, mid-pregnancy, and at 6-months postpartum. NFIs and breakfast time were estimated from 24-hour dietary recall interviews, and depressive symptoms were self-reported using the Center for Epidemiologic Studies Depression Scale. NFIs were categorized into three classifications to represent short, middle, and long NFIs. Longitudinal associations were evaluated using mixed effects linear models with interaction terms between NFIs and each timepoint. Results: NFIs remained largely stable at the group level across the three study visits (M [SD] = 12.7 [2.75] hours). Although NFIs were not significantly associated with depressive symptoms, long NFIs showed geometric mean ratio of 0.84 (95% CI: 0.64 to1.11) relative to middle NFIs at mid-pregnancy. Conclusions: NFIs and depression were not associated among this perinatal sample. Future studies should explore circadian eating patterns (e.g., the timing of the last eating episode relative to dim-light melatonin onset), different timepoints (e.g., late pregnancy), and pregnant individuals across the weight spectrum.

The satiety cascade includes post-prandial increases in plasma glucose and insulin, and changes in appetitive gut hormones, including decreases in orexigenic stomach-derived ghrelin, and increases in liver-foregut-derived LEAP2 hormone, a ghrelin antagonist. However, which contribute to post-prandial attenuation of eating behaviour with increasing preload meal size is unclear. In a randomised, single-blinded study, adults without obesity attended four visits, consuming 750mL liquid preloads 0, 600, 900, 1200 kcal, with assay of plasma glucose, acyl ghrelin (AG), LEAP2 and serum insulin over 0-3h with appetite ratings (n=17, 65 visits). At 2h a virtual portion size creation task measured desired food intake (n=15, 58 visits, after data exclusion), and at 3h an ad libitum meal measured actual food intake (n=11, 43 visits). The greater the pre-load meal size, the greater the post-prandial increase in plasma glucose and serum insulin, and greater the decrease in plasma AG and AG/LEAP2 ratio, associated with greater attenuation of eating behaviour (appetite ratings, desired/actual food intake). The strongest correlations of eating behaviour with blood measures were for serum insulin, plasma AG and AG/LEAP2 ratio, with weaker results for plasma glucose. Although there was a weak correlation of post-prandial plasma LEAP2 with pre-load meal size but not with eating behaviour. Post-prandial increases in serum insulin and decreases in plasma AG and AG/LEAP2 ratio appear part of the satiety cascade related to preload meal size in adults without obesity. Future studies should investigate potential mediation of satiety in this context via other appetitive gut hormones, and in obesity.

Context: Prader-Willi syndrome is a genetic neurodevelopmental disorder characterized by hyperphagia and early-onset obesity from hypothalamic dysfunction with endocrinopathies and learning disability. Management is challenging with strict control of the food environment needed. While newer glucagon-like peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited case reports in PWS. Objective/Design/Setting: Retrospective records review of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic. Patients: mean +/- SD age 28.3 +/- 10.1 years, 83% female, BMI 46.6 +/- 8.2kg/m2, 75% type 2 diabetes mellitus. Intervention: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once weekly (1.0-2.4). Results: Although there was no significant weight loss on semaglutide, there was stabilisation of the weight gain prior to treatment over previous 12.4 months (7.6-23.0) (post -3.1 +/- 9.9% vs. pre +5.7 +/- 5.6%: d -0.72, P=0.037). There was a significant decrease in hyperphagia on semaglutide from hyperphagia questionnaire for clinical trials (n=11, -7.3 +/- 6.1 (max 36), d -1.19, P=0.003), having been stable before treatment. HbA1c improved in those with elevated baseline levels (n=6, -4.2 +/- 4.9%, d -0.74, P=0.13). Mild gastrointestinal side effects were seen in 25% but did not lead to discontinuation. Conclusions: In adults with PWS, semaglutide produced weight maintenance, reduced hyperphagia, and improved glycaemic control, with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and adolescents with PWS, especially in those without T2DM, where efficacy may be greater.

Objective. This systematic review and meta-analysis synthesised the global prevalence of overweight and obesity in people with Down syndrome (DS) across the lifespan, characterised determinants of excess adiposity, and examined associations with adverse cardiometabolic outcomes. Methods. Six databases were searched without date or language restriction. Two independent reviewers screened studies, extracted data, and assessed quality using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. Prevalence was pooled using a random-effects logit model. A pre-specified subgroup analysis by age band was conducted. Publication bias was assessed with Egger's test and certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results. Twenty-six studies (7,840 individuals; 14 countries) were included. The pooled prevalence was 18% (95% CI 15-22%) in children and adolescents, 36% (95% CI 26-47%) in adults, and 30% (95% CI 20-43%) in mixed-age cohorts; the test for subgroup differences was significant. The overall pooled prevalence was 22% (95% CI 18-26%; prediction interval 7-53%; I^2 = 95.3%). No publication bias was detected (Egger's t = 0.39, p = 0.6964). DS-specific growth charts yielded estimates 14-37 percentage points lower than general-population references applied to the same cohorts. Obesity more than doubled obstructive sleep apnea risk (RR 2.4; 95% CI 1.34-4.34) and non-alcoholic fatty liver disease was present in 82% of obese versus 45% of non-obese children with DS. GRADE certainty was Moderate for prevalence estimates. Conclusions. Overweight and obesity in DS are highly prevalent, age-progressive, and substantially exceed general-population rates at every life stage. Roughly one in five people with DS is affected overall, rising to more than one in three adults. The reference chart applied is the single largest source of heterogeneity in reported estimates. Cardiometabolic surveillance, adapted lifestyle interventions, and primary prevalence research from low- and middle-income countries are the highest-priority gaps.

Background: As global obesity rates have increased, so too have efforts to manage obesity. This work estimates how many people maintain a lifelong healthy weight, have weight loss potential, and who successfully lose weight without medical support. Methods: Using the 1946 National Survey of Health and Development (1946NSHD; n=4,423), the 1958 National Child Development Study (1958NCDS, n=16,749) and the 1970 British Cohort Study (1970BCS; n=15,612), we quantify the prevalence of lifetime healthy weight, overweight and obesity by ages 51-55, and compare prevalence in early adulthood to the 2000-02 Millenium Cohort Study (2001MCS; n=9,675). We identified those who maintained, lost, gained, or cycled weight up to ages 50-55 (1958NCDS) and 46-54 (1970BCS), relative to their highest body mass index (BMI) before age 42, and examined predictors of group membership using multinomial regression models. Findings: In 1970BCS one-in-five people maintained a healthy BMI into their fifties, whilst 43% experienced obesity at least once, up from 25% in 1946NSHD. In 2001MCS 19% already had obesity by age 23, compared to 1-2% in the oldest cohorts. Across cohorts, those who maintained a healthy BMI were more socioeconomically advantaged, while those who experienced obesity were the most disadvantaged. Among those with obesity, a similar proportion lost weight in both cohorts (~13%), whilst 33-39% continued weight gain. Few potential drivers were associated with weight loss after adjusting for peak BMI, whilst socioeconomic disadvantage predicted further weight gain, as did the intention to lose weight. Interpretation: Weight loss from obesity is rare and the rate has remained consistent over time, whilst weight gain into obesity is common, and prevalence of lifetime obesity has increased.

Body mass index (BMI) alone may underestimate clinically relevant obesity because it does not capture central fat distribution. We compared obesity prevalence in Mexico using BMI-only criteria, adiposity-confirmed criteria, and the clinical obesity definition proposed by the Lancet Diabetes and Endocrinology Commission. We conducted a population-based, cross-sectional study of 13,160 adults aged 18 years or older who participated in the 2018-2019 Mexican National Health and Nutrition Survey (ENSANUT). Obesity prevalence was estimated through survey-weighted analyses that accounted for the complex sampling design. The weighted prevalence of obesity based on BMI was 34.5% (95% CI, 33.1-35.9), while 30.9% (95% CI, 29.6-32.2) met criteria for clinical obesity. One quarter of individuals with clinical obesity had a BMI under 30 kg/m2, a phenotype more common among older adults. Half of adults with a BMI under 30 kg/m2 showed elevated central adiposity. BMI alone underestimates clinically relevant obesity in Mexican adults. Adding waist-based measurements could improve the identification of individuals with excess fat and metabolic risk, both in clinical settings and population monitoring.

Abstract Introduction: Birthweight reflects fetal growth from conception. The complications arising from the extremes of fetal growth are well known, but addressing these effectively depends on understanding how and when fetal growth is affected by various maternal and fetal factors. We aimed to compare associations of fetal genetic and maternal environmental factors with fetal weight mid-pregnancy and birthweight. Material and methods: We studied 3110 mother-child pairs from three population-based birth cohorts (UK and China). Estimated fetal weight at ~20 weeks gestation (EFW20) and birthweight were the outcomes of interest. Exposures were fetal genetic factors (fetal sex and fetal birthweight genetic score [BW GS]) and maternal factors (maternal BW GS, BMI, fasting plasma glucose [FPG], smoking, age, and parity). Associations were studied using multivariable linear regressions within cohorts and meta-analysed. Results: All exposures were associated with both EFW20 and birthweight, apart from maternal FPG and smoking which were associated with birthweight only. Male fetal sex and a higher maternal BW GS were consistently associated with higher EFW20 and birthweight, whereas the fetal BW GS, maternal FPG, BMI and smoking showed more marked associations later in pregnancy. Maternal age and parity showed directionally opposite associations with EFW20 and birthweight. Conclusions: Fetal genetic and maternal environmental factors vary in their effect on fetal growth in mid-pregnancy compared with late pregnancy. These findings contribute to our understanding of growth across pregnancy and may inform the timing of clinical monitoring of fetal growth and interventions targeting modifiable maternal factors.

BackgroundObesity is a complex multifactorial disease associated with chronic low grade inflammation, gut microbiota dysbiosis, and impaired gut-brain communication. Oligomeric procyanidins from grape seed extracts (GSE) are promising prebiotic candidates, capable of modulating host metabolism through interactions with the gut microbiota. MethodsC57Bl/6J male mice were rendered obese by feeding them a high fat, high sucrose diet and were orally administered GSE at a dose of 1or 2 g/kg/day for 12 weeks. We assessed body weight, adiposity, glucose tolerance, insulin sensitivity, circulating hormones, brain homeostasis markers, colonic and liver gene expression, 16S rRNA gene sequencing of the gut microbiota profiles, and untargeted cecal metabolomics. ResultsGSE reduced body weight gain, visceral adiposity, adipocyte hypertrophy, and improved oral glucose tolerance and insulin sensitivity. It normalized circulating lipid and glucose levels and lowered fasting insulin and leptin while increasing endogenous GLP-1. Hepatic gene expression analysis revealed a dose-dependent restoration of antioxidant defenses (SOD, CAT) and lipogenic transcription factors (SREBP, ChREBP). In the colon, GSE attenuated pro-inflammatory IL6 cytokine expression and strikingly upregulated GLP-1 and GLP-1 receptor expression. Microbiota analysis revealed a profound, dose-dependent remodeling of gut microbiota composition and diversity, with an expansion of health-associated taxa, such as Akkermansia muciniphila. Brain analyses revealed restoration of NAA and BDNF levels together with markers consistent with improved mitochondrial function. Cecal metabolomics revealed normalization of secondary bile acid metabolism, restoration of arginine bioavailability, and reduction in the accumulation of L-DOPA and spermidine. ConclusionsAn oligomeric procyanidin-rich grape seed extract acts as a multitarget prebiotic that alleviates diet-induced obesity and is associated with coordinated restoration of gut microbiota composition, GLP-1 signaling, and gut-brain and gut-liver communication pathways. Convergent dose-dependent effects on Akkermansia muciniphila abundance, GLP-1, NAA, and BDNF identify key mechanisms underlying its metabolic benefits.

Objective: This systematic review and meta-analysis examined 1) the effects of stress management interventions on changes in stress eating for women, and 2) the longevity of these effects, by summarizing and assessing evidence from controlled and non-equivalent pretest-posttest intervention studies. Method: Five databases (PsycINFO, PubMed, Medline, Web of Science, CINAHL), existing sources, and grey literature were searched (February - June 2025). Studies that assessed stress eating or emotional eating, included a stress management intervention, and comprised at least 70% women were included. The primary outcome was reduction in stress eating. Data were pooled in meta-analyses using multi-level random-effects models and subset by follow-up period. Risk of bias was assessed via funnel plots and sensitivity analyses. Results: Sixty studies with 119 effect size estimates were included in the primary analysis. Pooled estimates indicated that stress management interventions significantly reduced stress eating (Hedges g = -0.4174, p < 0.001), with pre-post designs having larger effects than controlled trials. Subgroup analyses of follow-up periods found small effects in the short-term (before 3 months; Hedges g = -0.4202, p < 0.0001) and moderate effects for mid-term (3-6 months; Hedges g = -0.5886, p < 0.0001). Effects beyond 6 months were small and nonsignificant (Hedges g = -0.4370, p = 0.0660). Conclusion and Relevance: Stress management interventions appear to be effective for reducing stress eating for women, suggesting the potential to incorporate stress management in interventions targeting obesity. Effects may be only sustained 6 months post-intervention, suggesting the need for strategies to bolster long-term effectiveness.

Background: Vietnam and similar low-middle-income countries face a double/triple burden of overweight-obesity, thinness, and stunting. We examined how pre-pubertal BMI affects longitudinal height trajectories in a large Vietnamese cohort. Methods: We analyzed annual school health data from Hanoi, Ho Chi Minh City, and Haiphong (2018-2025). Children with greater than or equal to 3 visits (n = 40,887) were classified by WHO BMI category (thinness, normal, overweight, obesity) at sex-specific pre-pubertal index ages (males 11 years, females 9 years). Height trajectories were visualized via LOESS smoothing. Between-group differences were tested using Kruskal-Wallis with Dunn post-hoc tests and bootstrap median differences. BMI transitions assessed whether weight-status normalization recovered height potential. Results: At index ages, obese children were taller than normal-BMI peers (+5.1 cm at 11 years, peaking at +5.8 cm at 12 years for males and +4.0 cm at 9 years for females), while thin children were shorter (-3.0 to -4.2 cm). Differences narrowed progressively, becoming non-significant by 15 years in females (p = 0.885) and 17 years in males (p = 0.201). BMI normalization was associated with convergence toward normal-weight peers while persistent thinness showed no recovery. Results were consistent across ages, cities, and sensitivity analyses. Conclusions: Pre-pubertal BMI shapes the tempo, not outcome, of pubertal height gain, supporting early, sex-specific nutritional intervention without compromising adult height.

Obesity arises from interactions between several factors including physiology, environment and genes. Studies in humans have revealed that up to 70% of overweight and obesity can be attributed to biological and genetic factors. Thus, rodent models that capture innate susceptibility or resistance to obesity have been invaluable for disentangling inherent drivers of obesity from neurobiological alterations that occur in response to consumption of obesogenic foods and/or increased adiposity. For example, studies of rats selectively bred for their propensity vs resistance to diet-induced weight gain (DIO and DR) have uncovered differences in hypothalamic circuits involved in leptin signaling and revealed relationships between susceptibility to obesity and motivational response to food cues, as well as inherent and diet-induced alterations in mesocorticolimbic systems that differ between these populations. Maintaining selectively bred lines in a closed breeding population requires the periodic introduction of new genes to avoid inbreeding. Here we describe a process for maintaining these lines, characterize key phenotypes across the selection process and verify weight gain and obesity phenotypes in the resulting colony. In addition, given the central role of the striatum in motivation for food, we examined basal striatal function and food motivation in these refreshed lines using whole-cell patch clamping and instrumental procedures. Key weight and metabolic phenotypes were maintained in the resulting colony, as was enhanced motivation for food in obesity prone rats. This provides a strong basis for examination of interactions between genes, environment and neurobehavioral plasticity that promote weight gain and obesity.

Insulin resistance, an often-untreated precursor of type 2 diabetes mellitus (T2DM), is implicated in cognitive decline in adults, yet its impact on the developing brain in youth with obesity remains poorly understood. We investigate whether insulin resistance moderates the relation between hippocampal volume and unhealthy food-seeking in overweight and depressed youth ages 9-17 who completed an oral glucose tolerance test and a cognitive task assessing unhealthy food-seeking motivation at baseline, 6-, and 24-months follow-up, and structural MRI at baseline and 6-months follow-up. Insulin sensitivity moderated this relation: smaller baseline hippocampal subfield volumes predicted increased unhealthy food-seeking over 24 months (ps<0.05). Categorical grouping revealed subfield CA2/3 and 4 volumes predicted this relation among insulin-resistant (ps<0.05), but not insulin-sensitive (ps>0.10), youth, suggesting that threshold criteria for insulin resistance are physiologically meaningful. These findings identify a neuro-metabolic risk phenotype that precedes T2DM and may accelerate unhealthy food-seeking severity in youth with obesity.

Background: Yoga may support changes in dietary intake and/or physical activity levels, supporting sustainable weight loss. However, previous research has focused on yoga postures (asanas) rather than breathing practices (pranayama). This study used the proof-of-concept stage in the ORBIT model to evaluate feasibility, acceptability, and preliminary efficacy of a breath-based yoga program integrated within a behavioral weight loss (BWL) intervention. Methods: Fifteen participants with overweight or obesity (BMI: 31.3 +/- 4.3, 80% female) were enrolled in a 16-week, single-arm, group-based BWL intervention which included four breath-based yoga sessions/week, individualized daily goals for energy intake reduction, and progressive aerobic exercise recommendations. Primary outcomes included prespecified benchmarks enrollment, retention, adherence, and acceptability. Secondary outcomes included changes in body weight and composition, metabolic health indices (e.g., blood pressure, fasting glucose, abdominal obesity), physical activity, appetite, and dietary intake. Results: Mean percent weight loss was 6.5 +/- 6.0%, exceeding the pre-defined proof-of-concept benchmark. Recruitment and adherence exceeded established benchmarks, with mean in-class attendance of 84.1 +/- 14.6% and adherence to the prescribed duration of at-home yoga sessions averaging 85.5 +/- 38.4%. However, retention was lower than the pre-specified benchmark (73% vs 80%). Positive changes were observed in waist circumference, blood pressure, and appetite traits. Self-reported satisfaction with the program and outcomes were acceptable (mean ratings >6/10). Conclusions: A BWL with a breath-based, low-intensity yoga can lead to acceptable weight loss with potential benefits in key behavioral and metabolic health indices. Recruitment, high adherence, and satisfaction demonstrated feasibility.

Background: Poor prenatal sleep health is associated with greater gestational weight gain, but the contributions to longer-term maternal weight retention remain unclear. Purpose: To examine associations between prenatal sleep health across multiple domains and maternal weight retention 2 to 7 years after a first birth. Methods: Participants were from the nuMoM2b-Heart Health Study. Self-reported sleep was assessed during early (6 to 13 6/7 weeks) and mid-pregnancy (22 to 28 6/7 weeks) across six domains: regularity, quality, sleepiness, timing, efficiency, and duration. A multidimensional sleep health (MSH) score reflected the number of domains meeting healthy thresholds. Outcomes included maternal weight retention, total and substantial (>11 lbs.), from pre-pregnancy to 2 to 7 years after a first birth. Associations were estimated using adjusted linear regression for total weight retention and Poisson regression with robust variance for substantial weight retention. Results: The sample included 3,661 individuals with data in early (n = 2,962) and mid-pregnancy (n = 3,210). In early pregnancy, healthy sleep duration was associated with lower total weight retention, whereas healthy sleep regularity was unexpectedly associated with greater retention. In contrast, during mid-pregnancy, a higher MSH score was associated with a lower risk of substantial weight retention (RR = 0.96, 95% CI: 0.93 to 0.99). Healthy sleep duration and quality were the two individual domains associated with lower weight retention (2 to 3 lbs.). Conclusions: In a prospective cohort of pregnant nulliparous individuals, healthy prenatal sleep, particularly during mid-pregnancy, was associated with less maternal weight retention 2 to 7 years after delivery. Future studies should estimate the causal effects of sleep health on long-term maternal weight retention.

ABSTRACT IMPORTANCE Childhood obesity is a growing global health concern associated with adverse physical, psychiatric, and neurodevelopmental outcomes. Although previous neuroimaging studies have linked obesity to widespread alterations in brain structure and function, it remains unclear how well multimodal neuroimaging measures and genetic markers can predict future weight gain and inform early intervention strategies. OBJECTIVE To evaluate the predictive utility of multimodal MRI measures and polygenic risk scores for obesity in estimating proportional body weight at baseline and predicting weight gain over one year in preadolescent children. DESIGN, SETTING, AND PARTICIPANTS This study used data from the Adolescent Brain Cognitive Development (ABCD) Study, a large-scale, multisite longitudinal cohort of children aged 9 to 10 years (N = 11,880). Analyses included baseline data collected between 2016 and 2018, and one-year follow-up data collected between 2018 and 2020 across multiple imaging sites. MAIN OUTCOMES AND MEASURES Elastic net regression models were applied to structural MRI (including diffusion tensor imaging) and resting-state functional MRI data to predict baseline triponderal mass index (TMI), a weight-for-height measure that more accurately reflects adiposity in children than body-mass index (BMI). Longitudinal classification models were developed to predict excess weight gain relative to normative developmental trajectories at one-year follow-up. Models were evaluated with and without the inclusion of polygenic risk scores and other non-imaging covariates. Generalizability was assessed using leave-one-site-out cross-validation. RESULTS Structural MRI measures predicted baseline TMI with an R^2 of 0.21, whereas resting-state functional MRI measures predicted TMI with an R^2 of 0.08. Classification models predicted one-year weight gain with area under the receiver operating characteristic curve (AUC) values of 0.73 for structural MRI and 0.60 for resting-state functional MRI. Including polygenic risk scores and other covariates improved model performance (structural MRI: R^2 = 0.25, AUC = 0.75; resting-state functional MRI: R^2 = 0.15, AUC = 0.69). Leave-one-site-out cross-validation revealed reduced generalizability across imaging sites (structural MRI R^2 = 0.13-0.17; resting-state functional MRI R^2 = 0.02-0.09; structural MRI AUC = 0.73-0.74; resting-state functional MRI AUC = 0.60-0.67). CONCLUSIONS AND RELEVANCE Multimodal MRI measures were associated with proportional body weight and demonstrated modest predictive utility for future weight gain in preadolescent children, explaining up to one fifth of the variance in weight-related outcomes. The addition of genetic and non-imaging variables improved prediction accuracy, underscoring the multifactorial nature of childhood obesity. However, the observed decline in performance under site-wise cross-validation highlights the need to address site-related variability to enhance reproducibility and generalizability in neuroimaging-based predictive models of pediatric obesity.

IntroductionAnorexia nervosa (AN) is more prevalent in women than men, although rates in men are rising. Animal models can provide insight into whether this differential prevalence is rooted in biological mechanisms, but prior studies have yielded conflicting findings. Using the activity-based anorexia (ABA) model, we previously demonstrated that female mice exhibit distinct vulnerable and resilient phenotypes. Here, we use this phenotypic framework to investigate sex differences in ABA susceptibility. MethodsWe tested young adult male C57BL/6N mice using the same ABA protocol used to test age-matched C57BL/6N females. Individual differences in daily bodyweight, food intake, water intake, and wheel running were analyzed and compared across sexes. ResultsMales exhibit the same vulnerable and resilient phenotypes as females, with no sex difference in the proportion of mice exhibiting each phenotype or the repertoire of behaviors characterizing them. In both sexes, vulnerable mice exhibit catastrophic weight loss driven by excessive light cycle running, while resilient mice exhibit weight stabilization driven by adaptive changes in consumption. Running during the feeding window revealed that vulnerability is not driven by a decision to run instead of eat in either sex. ConclusionsABA models adaptive and maladaptive responses to food restriction in both sexes. Behavioral responses to starvation are similar across sexes, suggesting that sex differences in AN prevalence may be driven by stronger sociocultural pressures faced by women to lose weight.

Early-life exposures during critical periods of development significantly impact lifelong metabolic risk and likely contribute to the rising rates of obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in children. Here, we evaluated the safety and metabolic effects of semaglutide, a GLP-1 receptor agonist (GLP-1 RA), administered from preconception through lactation in dams fed a high-fat diet (HFD) or standard diet, and assessed metabolic outcomes in dams and their offspring. Offspring were weaned to a standard diet. We found that semaglutide improved body composition and glucose metabolism in HFD-fed dams during pregnancy. These maternal changes persisted 10 weeks after weaning despite discontinuation of semaglutide treatment. HFD exposure impaired glucose homeostasis and promoted hepatic steatosis in offspring at 18 weeks. These effects were ameliorated by maternal semaglutide treatment. Importantly, metabolic improvements in dams and offspring occurred without adverse effects on conception rate or fetal viability. These findings suggest that GLP-1 RA during the perinatal period can improve maternal and offspring metabolic health in a mouse model of obesity and support further investigation of GLP-1-based therapies to mitigate maternal metabolic dysfunction and improve metabolic risk in children. ARTICLE HIGHLIGHTS* Rates of obesity, type 2 diabetes, and fatty liver disease are rising in children, in part due to maternal obesity and insulin resistance that program offspring metabolic risk during the perinatal period. * We asked whether the GLP-1 receptor agonist (GLP-1 RA), semaglutide, administered during critical developmental windows could prevent adverse outcomes in offspring using a diet-induced mouse model of maternal obesity. * Semaglutide, given to dams from preconception through lactation, improved maternal metabolism and ameliorated metabolic dysfunction in offspring caused by maternal high-fat diet. * These findings highlight a potential role for perinatal GLP-1 receptor agonism to improve maternal metabolic health and reduce metabolic risk in offspring.