Obesity

Background: C-terminal binding protein 2 (CtBP2) has been implicated in metabolic regulation, but its association with specific measures of adiposity and lipid profiles in humans remains unclear. This study examined the relationship between circulating CtBP2 levels and key components of metabolic syndrome, focusing on body fat distribution and lipid markers. Methods: Data from 508 participants (259 men, 249 women) from a publicly available dataset were analyzed. Serum CtBP2 concentrations were measured using ELISA. Associations with obesity markers (BMI, waist circumference, waist-to-hip ratio) and lipid profiles (triglycerides, HDL cholesterol) were assessed using Spearman correlation and linear regression, adjusting for age and sex. Results: CtBP2 levels showed weak but statistically significant positive correlations with all measures of adiposity, with the strongest association observed for waist circumference ({rho} = 0.150, p < 0.001), followed by BMI ({rho} = 0.120, p = 0.007) and waist-to-hip ratio ({rho} = 0.098, p = 0.027). No significant correlations were found with triglycerides or HDL cholesterol. In the regression model predicting BMI, age, and sex were significant predictors, while CtBP2 demonstrated a trend toward association ({beta} = 0.080, p = 0.052). Conclusion: Circulating CtBP2 appears to be modestly associated with measures of adiposity, particularly abdominal fat, but not with lipid abnormalities. These findings suggest a potential role for CtBP2 in obesity-related metabolic dysregulation and underscore the need for further mechanistic studies to clarify its clinical relevance.

Background: Repeated metabolic-bariatric surgery (MBS, r-BS) represents 10-25% of all MBS procedures and is commonly performed for recurrent weight gain after initial weight loss. How weight loss followed by regain reshapes adipose tissue biology remains unclear. We hypothesized that women undergoing r-BS exhibit a distinct adipose tissue signature compared with those undergoing primary bariatric surgery (p-BS). Methods: We analyzed subcutaneous and visceral adipose tissues (SAT, VAT, respectively) from women undergoing either p-BS, or r-BS with documented >15% weight loss after prior MBS. Tissues were assessed histologically, molecularly, and functionally (activation of human microglia cells (HMC3) by SAT secretome). Results: Consistent with other cohorts, women undergoing r-BS (n=21) trended to be older (47.2 vs. 40.5 y, p=0.06) than those undergoing p-BS (n=35), with a lower BMI (42.3 vs. 45.6 kg/m2, respectively, p=0.103), and a trend for improved cardiometabolic risk parameters such as fasting insulin, CRP and HDL-c. Adipose tissue histological features (adipocyte size, fibrosis, macrophage and crown-like structure abundance) were similar, while adipose mast cells were slightly (though insignificantly) more prevalent in r-BS. A single-nucleus RNA-seq-based deconvolution algorithm applied to bulk RNA-seq confirmed the absence of a major shift in adipose tissue cell-type composition. Yet, it uncovered a unique SAT transcriptome, with activation of inflammatory pathways in r-BS. Consistently, SAT explants from r-BS secreted higher protein concentrations of NFkB-regulated cytokines IL6 and IL8. Biological impact of the more inflammatory secretome was demonstrated by its increased ability to activate human microglia cells. Conclusions: Prior BS with significant weight loss-regain in women is associated with an inflammatory SAT transcriptome and secretome, possibly reflecting altered adipose-brain endocrine communication.

Background: 39M children worldwide are overweight or have obesity, accelerating risk for adult non-communicable diseases. Presently, interventions to prevent obesity have had limited success due to poor timing and lack of personalisation. Objective: We aimed to identify early-life predictors of childhood obesity (ChOB) that could aid targeting specific population subsets for obesity prevention interventional studies. Methods: Data were from the Raine Study Gen2 participants (n=1494). Anthropometric and genetic predictors evaluated included birthweight (BW), early-life BMI (1-3 years), and three polygenic scores (PGS) [two BW-PGSs (BW-PGS2016 and BW-PGS2019) and a ChOB-PGS], developed from BW and ChOB genome-wide-association-studies, respectively. Multivariate analyses were performed to investigate associations between predictors and child-BMI (5-, 8-, 10-years). Results: BW-PGS2019 associate with child-BMI at 5-years. BW-PGS2016 was not associated with child-BMI. Remaining predictors positively associate with child-BMI at 5-, 8- and 10-years (p<0.001). Early-life BMI, ChOB-PGS and BW accounted for up to 38.7%, 5.8% and 3.4% of the variability in child-BMI, respectively. Conclusions: Our data suggest early-life BMI is a better predictor of child-BMI than ChOB-PGS, and BW, accounting for up to ten-fold more variance in child-BMI. Future interventional studies to mitigate obesity could target early-life BMI as a marker to identify children at the highest risk.

Obesity is considered a risk factor for metabolic diseases, including type 2 diabetes, and results from an imbalance between energy intake and energy expenditure. While pharmacological approaches such as tirzepatide, a dual GIP/GLP-1 receptor agonist, effectively reduce food intake and body weight, strategies that enhance energy expenditure (EE) may provide complementary metabolic benefits. Intermittent cold exposure (ICE) is one such approach that enhances EE and improves glucose homeostasis independent of weight loss. However, the combined effects of these interventions remain unexplored. In this study, we investigated the individual and combined effects of tirzepatide and ICE on body composition, energy metabolism, and glucose homeostasis in diet-induced obese (DIO) male and female mice housed at thermoneutrality. After 8 weeks of 45% high-fat diet feeding, mice received tirzepatide (10 nmol/kg) or vehicle and were exposed to ICE (4{degrees}C, 1 h/day, 5 days/week) or remained at thermoneutrality for 3 weeks. Energy expenditure and substrate utilization were assessed using indirect calorimetry at thermoneutrality and during an acute 1 h cold challenge. Tirzepatide reduced body weight, food intake, and adiposity in both sexes, with a greater reduction in lean mass in males. ICE did not affect body weight but improved glucose homeostasis. At thermoneutrality, tirzepatide did not alter total EE but lowered respiratory exchange ratio (RER), indicating a shift toward lipid utilization. In contrast, ICE increased energy expenditure and fat oxidation, with no additive effects observed when combined with tirzepatide. Together, these findings highlight that targeting both energy intake and expenditure represents complementary, but not necessarily additive approaches to improving metabolic health.

Introduction: Managing gestational weight gain (GWG) is crucial for the health of mothers and their children. Mobile applications (apps) specifically designed for pregnancy are emerging as modalities to deliver accessible lifestyle intervention at a low-cost. However, current studies are varied in results and suffer from heterogeneity. Thus, we conducted this systematic review and meta-analysis to summarize the efficacy of mobile apps in managing GWG and investigate variables that may contribute to heterogeneity. Methodology: Seven databases were systematically searched up to 9 November, 2024. Only randomized controlled trials (RCTs) were included. Outcomes were excessive GWG and inadequate GWG according to the 2009 Institute of Medicine (IOM) guideline. Quality appraisal was performed using the Cochrane Risk of Bias 2 (RoB 2) tool. Random-effect model meta-analysis was conducted using odds ratio (OR) as the summary measure alongside their 95% confidence intervals (CI). Results and Discussion: Fifteen RCTs were included. Mobile apps led to a significant overall decrease in excessive GWG (OR: 0.71; 95% CI: 0.54 to 0.95; p-value: 0.02; I2: 60%). Subgroup analysis showed that social media apps, self-monitoring functionalities, and overweight/obese patients are associated with a significant reduction in excessive GWG. However, there was significant evidence of small-study bias in the analysis. Moreover, mobile apps also significantly increased inadequate GWG (OR: 1.51; 95% CI: 1.04 to 2.21; I2: 0%). Meta-regression did not reveal any significant finding. Conclusion: In conclusion, mobile app interventions are shown to be effective in preventing excessive GWG, particularly social media apps and those with self-monitoring functionalities. However, the reduction in excessive GWG may only be seen in overweight and obese patients and more studies are needed to ascertain this finding. Lastly, mobile apps are associated with an increased risk of inadequate GWG and strategies to combat inadequate GWG are needed.

BackgroundObesity arises from a complex interplay of genetic and environmental factors, with alterations of transcriptional networks that integrate metabolic, immune, and regulatory pathways. Conventional measures such as body mass index (BMI) quantify body size but fail to capture the molecular heterogeneity underlying divergent metabolic outcomes. We therefore sought to construct a gene expression-based transcriptomic representation of obesity, using BMI as a practical training anchor, and to use this framework to delineate transcriptional programs associated with metabolically healthy and pathogenic obesity, with subsequent projection to mouse transcriptomic data for cross-species validation. MethodsTranscriptome data of human visceral adipose tissue (N= 1,298) were used to derive the transcriptomic BMI model, and genes contributing to the model were functionally annotated by gene set enrichment analysis. The human-trained model was subsequently applied to mouse selection lines (N = 18) with divergent obesity phenotypes. In the human cohort, post hoc stratification into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) groups was performed using a downstream classification framework incorporating observed BMI together with predicted BMI, to assess whether model-derived predicted BMI reflected obesity-related pathophysiologic status. ResultsModel-selected genes were involved in coordinated regulation of lipid metabolism, immune activation, and growth signaling, extending to mitochondrial and translational pathways. Cross-species analyses uncovered conserved metabolic polarization: DU6 mice exhibited lipid-anabolic and inflammatory remodeling, whereas DU6P mice displayed oxidative, mitochondrial, and GH-axis-enriched transcriptional states. In human cohorts, MHO individuals showed upregulation of mitochondrial energetics and protein synthesis, while MUO individuals were characterized by increased autophagy, lipid catabolism, and stress-adaptive signaling on the transcriptional level. Together, these findings define a conserved molecular continuum linking oxidative efficiency to metabolic health and inflammation to metabolic vulnerability. ConclusionsThis integrative transcriptomic framework bridges human and mouse adipose biology to uncover conserved mechanisms underlying obesity phenotypes. By contrasting mitochondrial and translational programs with inflammatory and catabolic pathways, it provides mechanistic insight into metabolic resilience and a foundation for precision approaches to obesity management.

Major international sporting events frequently impose exogenous demands that challenge adult circadian rhythms, often leading to the misalignment of sleep-wake cycles and social schedules. This cross-sectional study investigated the impact of the FIFA 2022 World Cup on adult sleep patterns to assess the prevalence and determinants of tournament-associated circadian disruption. Through an online survey, we captured data on sleep duration, timing, and subjective quality from a diverse adult population using Pittsburgh Sleep Quality Index (PSQI) score. The results indicate that 81.3% had high problematic sleep according to PSQI scores, while only 9% perceived that their sleep pattern was impacted by watching matches during the tournament. While 83.7% of the participants had low or mild anxiety according to GAD-7 scores, we found that GAD-7 scores correlated significantly with PSQI scores. Married participants had significantly lower PSQI scores (RR 0.856, p = .005), while those who reported that their sleep hours had changed during the tournament had significantly higher PSQI scores (1.180, P-value <0.001). Males reported a significantly high impact of the tournament on their sleep (OR 2.622, P-value <0.001). In conclusion, our data demonstrate a discrepancy between self-perception of sleep quality and self-rated assessment by PSQI scores, as well as the substantial impact of major international sporting events on adult sleep hygiene. The results provide data-driven insights helpful in evaluating potential circadian risks and informing public health strategies for major sporting events such as the FIFA world cup.

Background Early onset obesity in children, almost always accompanied by significant health complications, may be driven by rare genetic variants that influence appetite, metabolism, and nutrient absorption. Traditional treatment approaches are usually insufficient for those with monogenic obesity of this type. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, and related drugs such as melanocortin 4 receptor agonists, have emerged as promising first-line treatments for severe obesity. There is no established protocol or pathway in England for identifying children with monogenic obesity who could benefit from these and similar treatments Methods We undertook early economic modelling to examine the cost-effectiveness, from a health service perspective, of implementing a new pharmacotherapeutic care pathway for the identification and treatment of monogenic obesity in children. We modelled a hypothetical population of children with hyperphagia and body mass index (BMI) three standard deviations above mean values for age and sex. We evaluated the clinical decision to initiate the pathway using a decision tree model with patient quality-adjusted life years (QALYs) and NHS healthcare costs 12 months from an initial clinic visit as outcomes, and calculated incremental cost effectiveness ratios and a cost-effectiveness acceptability curve. Results Both costs and QALYs were higher under further investigation (GBP3,247 and 0.47 QALYs) compared to no further investigation (GBP1,589 and 0.24 QALYs). The incremental cost-effectiveness ratio in the base case was GBP7,133 per QALY. Further examination of these children was therefore likely to be cost effective in this model. Conclusion A decision-tree model suggested that further investigation of severely obese children potentially eligible for treatment with semaglutide is likely to be cost-effective for the NHS. However, this result is associated with uncertainty arising from a lack of evidence for many key model parameters.

Objectives To examine the acute effects of a single bout of high-intensity interval training (HIIT) on fetal blood flow distribution during the third trimester of pregnancy. Methods Thirty-four healthy pregnant participants (mean age 31.6 years, standard deviation (SD) 4.1; gestational week 33.8 (SD 0.4) completed eight 30-second high-intensity cycling work-bouts interspersed with 2-minute rest periods. Fetal heart rate (FHR), maternal blood pressure, and Doppler-derived blood flow indices in the middle cerebral artery, umbilical artery and vein, and ductus venosus were assessed before and after exercise. We estimated fetal liver blood flow and the ratio of umbilical vein flow to ductus venosus. Maternal heart rate (HR) and FHR were recorded throughout exercise. Paired t-tests compared pre- and post-exercise values. Results No significant changes were observed in fetal blood flow indices or distribution following exercise. Average maternal HR and FHR during the work-bouts were 158 bpm (SD 16) and 152 bpm (SD 12), respectively. Following HIIT, maternal systolic blood pressure increased by 5 mmHg (95% CI 1 to 8, p=.014), maternal HR by 22 bpm (95% CI 15 to 28, p<.001), and FHR by 13 bpm (95% CI 10 to 17, p<.001). We recorded 16 instances of FHR above normal range during HIIT. Conclusion A single HIIT session in late pregnancy increased maternal blood pressure and HR and transiently elevated FHR but did not affect fetal blood flow indices or distribution. Brief episodes of fetal tachycardia were observed but appeared to be clinically insignificant. Future research should investigate the effects of repeated HIIT exposure during pregnancy.

Background: Obesity is a global health crisis, contributing to chronic diseases such as diabetes, cardiovascular disease, and metabolic syndrome. Traditional Chinese Medicine (TCM) has been used in East Asia to manage obesity, but evidence on its efficacy and safety remains limited. This systematic review and meta-analysis assess clinical evidence from randomized controlled trials (RCTs) on TCM for obesity treatment. Methods: We systematically searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to April 2026. Eligible RCTs compared TCM interventions with placebo or conventional treatments in obese patients. Two reviewers independently conducted screening, data extraction, and quality assessment. Meta-analysis was conducted using a random-effects model to calculate pooled weighted mean differences (WMD) and odds ratios (OR) for body weight, BMI, waist-to-hip ratio (WHR), lipid profiles, and adverse events. Results: A total of 33 randomized controlled trials (RCTs) involving 3,053 participants were included in the analysis. TCM significantly reduced body weight (WMD = -5.86 kg, 95% CI: -7.51 to -4.21), BMI (WMD = -2.82 kg/m{superscript 2}, 95% CI: -3.38 to -2.25), and WHR (WMD = -0.04, 95% CI: -0.06 to -0.02). Lipid profiles improved, with reductions in total cholesterol (WMD = -0.82 mmol/L), triglycerides (WMD = -0.65 mmol/L), LDL-C (WMD = -0.39 mmol/L), and increased HDL-C (WMD = 0.29 mmol/L) (all p < 0.001). Adverse events were infrequent, with no significant difference observed between TCM and control groups (OR = 0.51, 95% CI: 0.24 to 1.08). Funnel plots indicated no publication bias. Conclusion: TCM appears effective in reducing body weight and improving lipid profiles in obese patients, with a low incidence of adverse events. It may serve as a complementary treatment for obesity, though further high-quality RCTs are needed to confirm these findings and assess long-term outcomes.

ObjectivesLow serum testosterone (T) in men with obesity suggesting T deficiency may be misinterpreted by confounding changes in serum SHBG, Ts circulating carrier protein. Measuring or calculating "free" testosterone (FT) concentrations to define a low T is problematic as cFT is not a valid analytical variable lacking certified standard, quality control or reference range. We developed a novel metric, Scaled Testosterone (ST), comparing standardized serum T (LCMS) and SHBG without invoking hypothetical serum T fractions. MethodsSerum T and SHBG in men (n=10,027) pooled from three population-based studies in Australia were expressed as standardized (Z) scores (ZT, ZSHBG) and their difference ST = ZT-ZSHBG. ST was evaluated in a clinical trial of 51 men with severe obesity undergoing 1 year of diet-induced weight loss. ResultsZT and ZSHBG displayed linear correlation (r=0.44, 10-11) with ST approximating zero (-0.33 {+/-}2.14 SD). In non-obese men with low serum T suggestive of organic hypogonadism displayed very low ST indicating ST can evaluate whether a low serum T is proportionate to a concomitant serum SHBG. In men with obesity, low pre-treatment serum T and SHBG both increased during diet-induced weight loss with no change in serum LH while ST which remained within standard limits at each time. ConclusionsThe low serum T in men with obesity may better be considered as the pseudo-hypogonadism of obesity comprising low serum T with proportionately low serum SHBG in the presence of normal serum LH {+/-} FSH serving as a tissue androgen sensor.

Background/ObjectivesHuman plasma lipidomics provides valuable information on dietary and metabolic phenotypes, but the interpretation of high-dimensional lipid datasets remains challenging. We developed the Nutritional-Metabolic Lipid Profile (NMLP) module within LipidOne to translate plasma lipidomics data into interpretable nutritional-metabolic indices, functional categories, visual outputs, and biological statements. Subjects/MethodsNMLP calculates lipid indices reflecting cardiometabolic lipid status, fatty acid remodelling, overall lipid quality, oxidative protection, and omega-3/essential fatty acid status. The module was applied to three human plasma lipidomics public datasets: a randomized crossover glycemic-load feeding study, a eucaloric high-fat diet intervention in normal-weight women, and a large public dataset stratified by insulin sensitivity. ResultsAcross datasets, NMLP converted complex lipidomic matrices into coherent nutritional-metabolic profiles. In the glycemic-load study, the module highlighted metabolic lipid shifts not captured by standard clinical lipid panels, mainly involving cardiometabolic lipid status, oxidative protection, and fatty acid remodelling. In the high-fat diet intervention, NMLP tracked temporal lipid remodelling across pre-diet, on-diet, and post-diet states, consistent with metabolic adaptation to increased dietary fat exposure. In the insulin-sensitivity dataset, insulin-resistant subjects showed a storage-oriented lipid phenotype characterized by increased neutral lipid storage indices and altered lipid quality and oxidative-protection features. Category-level clustering further revealed heterogeneous nutritional-metabolic states within insulin-resistant subjects. ConclusionsNMLP provides a deeper and clearer interpretative framework for human plasma lipidomics in nutrition and metabolic health research. By translating lipid species into functional indices and category-level readouts, the module may facilitate the use of lipidomics in clinical nutrition, metabolic phenotyping, and precision nutrition studies. NMLP is freely accessible as part of the online LipidOne platform.

Background: Obesity is globally recognized as a complex, multifactorial chronic disease, with biological, psychological, environmental and behavioural factors involved in both disease pathogenesis and maintenance. Although previous group-based studies demonstrated involvement of each of these factors, there is large inter-individual variability in the factors contributing to disease development as well as intervention outcomes, causing limited translatability to the individual level. This heterogeneity in treatment effectiveness might be due to differential causal and maintenance factors of obesity. To enable the transition from a one-size-fits-all approach to a more personalized approach for individuals with overweight or obesity, this study aims to investigate if and how the degree of weight loss and changes in daily life behaviour after a combined lifestyle intervention depend on individual baseline profiles comprising of person characteristics, biological, psychological, environmental and behavioural factors. Methods: This study will include 600 individuals varying in BMI, 200 participants with a healthy BMI (18.5-24.9kg/m2), 200 with overweight (BMI 25.0-29.9kg/m2), and 200 with obesity (BMI [&ge;]30.0kg/m2). For all participants, a comprehensive individual baseline profile is created, including person characteristics, biological, psychological, environmental and behavioural factors. A clustering method is applied to identify clusters of participants with similar characteristics. Next, we examine if and how these clusters are linked to bodyweight indicators measured at baseline, and how they relate to daily lifestyle behaviour, as measured by ecological momentary assessment (EMA) using a smartphone app and sensor technology (3-week measurements). Individuals with overweight or obesity will be randomized to the intensive lifestyle intervention or a lifestyle information condition, to determine if treatment response can be predicted based on cluster characteristics, how daily lifestyle behaviour changes after an intervention, and how changes in daily lifestyle behaviour relate to treatment response. Discussion: The End of Average study aims to characterize a large set of individuals varying in body weight to predict intervention effectiveness measured as changes in body weight indicators and in daily lifestyle behaviours. If reliable predictors of treatment success can be identified, these can be applied in personalized lifestyle interventions to improve lifestyle behaviour, body weight management and overall health.

Objective Fatty Acid esters of Hydroxy-Fatty Acids (FAHFAs) are anti-diabetic and anti-inflammatory lipokines produced mainly by adipose tissue (AT). As exercise training enhances FAHFA levels, we investigated the impact of acute exercise (AE) and exercise-mimicking conditions on circulating and adipocyte FAHFA levels. Methods Clinical trial (NCT05572905) in 60 women, grouped by BMI (lean vs. obese) and age (young vs. older), was combined with in vitro experiments on human adipocytes. Following baseline characterization (body composition, VO2max, insulin sensitivity, AT/plasma FAHFAs), women underwent a cross-over AE and control interventions with repeated blood sampling for FAHFA analysis. Results In AT, lean and older women exhibited higher FAHFA levels than obese and young women, respectively; older women also showed a shift toward higher levels of 13/12-carbon-branched FAHFAs. Circulating FAHFA levels were similar across all groups and were not positively associated with insulin sensitivity, VO2max or FAHFA levels in AT. Although AE increased circulating free fatty acids (FFA), plasma FAHFAs dropped in response to both AE and control interventions. In adipocytes, FAHFAs were unaffected by glucocorticoids but increased in response to lipolysis together with gene expression related to FFA oxidation (FAO). Nevertheless, blocking mitochondrial FAO partially mimicked the lipolytic effect, while peroxisomal inhibition synergistically boosted FAHFA lipolysis-driven production despite having no effect alone. Conclusions While adiposity and aging modulate FAHFA levels in AT, circulating levels remain stable and unaffected by AE, challenging subcutaneous AT as their primary systemic source. In vitro, FAHFA synthesis is driven by high FFA availability but limited by competing peroxisomal FAO.

Background and ObjectivesChildren with Down syndrome (DS) have a high prevalence of obstructive sleep apnea (OSA) due to anatomic, neuromuscular, immunological and metabolic factors, yet the contribution of the tonsillar microbiome to airway obstruction in this population remains unexplored. We hypothesized that DS-associated OSA would be associated with a distinct tonsillar microbiome compared to non-DS OSA. MethodsTonsillar tissue from 22 DS and 18 NDS participants were analyzed by 16S rRNA sequencing. Alpha and beta diversity were assessed using Faiths phylogenetic diversity and UniFrac distances, respectively, and significantly different taxa were identified with ANCOM-BC and Mann-Whitney testing. ResultsAlthough overall microbial richness and community structure were similar between groups, overweight DS participants demonstrated increased phylogenetic diversity compared to normal-weight DS peers. Taxonomic profiling of the entire patient cohort revealed that in DS tonsils there were selective alterations in key genera with selective depletion of Haemophilus and enrichment of Staphylococcus, Rothia, and Lactobacillales. Haemophilus abundance correlated positively with tonsil weight in both cohorts. ConclusionsThese findings suggest that while global diversity is preserved, specific microbial shifts distinguish the DS tonsillar niche, potentially reflecting altered immune and metabolic environments associated with trisomy 21. Understanding these microbial differences may reveal mechanisms underlying the higher incidence and persistence of OSA in DS and inform targeted therapeutic strategies.

Background Insomnia symptoms are common in older adults. While observational studies suggest physical activity (PA) timing affects health outcomes, its effect on sleep remains unclear. We compared morning versus evening PA effects on insomnia severity and sleep quality in older adults with insomnia symptoms. Methods Eligible participants were aged 60 to 80 years with (sub)clinical insomnia (Insomnia Severity Index [ISI] score [&ge;]10). In a randomized cross-over trial, participants engaged in coached PA in the morning (10:00 - 11:00) or evening (19:30 - 20:30) for 14 days each. ISI scores were assessed post-intervention. Objective sleep parameters; duration, latency, efficiency, and timing, were assessed with a Withings Sleep Analyzer under the mattress. Subjective sleep quality was reported daily via smartphone app. Salivary dim light melatonin onset (DLMO) was measured on the final day of each intervention. Results Of 37 participants (mean ISI 14.3 {+/-} 3.3), 27 completed the study (mean age 69.8 {+/-} 5; 63% women). ISI scores improved after both morning ({Delta} - 2.5; 95% CI: - 1.14, - 3.83) and evening ({Delta} - 2.0; 95% CI: - 0.63, - 3.38) activity relative to baseline, but were not different between interventions. Compared to evening activity, sleep midpoint occurred earlier with morning activity (03:40 vs 04:00; {Delta} - 20 min; 95% CI: - 31, - 8). No differences in subjective sleep quality or DLMO were found. Exploratory analyses suggested insomnia scores improved specifically in late chronotypes following morning activity. Conclusions While morning vs. evening PA timing did not impact most sleep quality measures, it influenced sleep timing. Larger studies are needed to define optimal and personalized PA timing for improving sleep.

Background: Hypertensive disorders of pregnancy contribute substantially to maternal morbidity and mortality, and occur with increased frequency among women with uterine fibroids. Biomarkers involved in oxidative stress and endothelial function, including folate, vitamin B12, vitamin D, and homocysteine, have been studied in relation to hypertensive disorders of pregnancy, but their relationship to fibroid-associated risk has not been well characterized, particularly in racially and ethnically diverse populations. Study Design: This study was a retrospective analysis of the Boston Birth Cohort, a prospective cohort recruited at a large urban medical center. The analytic sample included 722 women with complete data on hypertensive disorder status, uterine fibroid status, and plasma biomarker measurements. Uterine fibroids and hypertensive disorders of pregnancy were ascertained through physician-assigned diagnostic codes and ultrasound report review. Plasma folate, vitamin B12, vitamin D, and homocysteine were measured in maternal or cord blood and analyzed as continuous variables and quartiles. Multivariable logistic regression models were used to estimate independent associations, evaluate interaction terms, and assess joint exposure categories. Results: Of the 722 participants, 12% (86/722) had uterine fibroids and 10% (72/722) had a hypertensive disorder of pregnancy. Plasma micronutrient concentrations did not differ significantly by fibroid status. Women with hypertensive disorders of pregnancy had higher plasma homocysteine concentrations compared with those without (p=0.028). Hypertensive disorders of pregnancy were more common in the lowest folate quartile compared with the highest quartile (p=0.018) and in the highest homocysteine quartile compared with lower quartiles (p=0.031). In joint-effects analyses, higher odds of having a hypertensive disorder of pregnancy were observed among women with both uterine fibroids and low folate compared with women without fibroids and with adequate folate (p=0.027). No significant joint associations were observed for vitamin D, vitamin B12, or homocysteine. Conclusion: In this cohort, the co-occurrence of uterine fibroids and lower folate concentrations was associated with hypertensive disorders of pregnancy. This joint exposure delineates a subgroup that may be clinically relevant for future studies aimed at refining maternal risk characterization and exploring targeted nutritional supplementation strategies.

Weight cycling (WC), defined as weight gain, loss, and regain, is common in obesity, but its metabolic consequences remain unclear. We tested whether WC-aggravated glucose intolerance in obesity is age-dependent and linked to circadian disruption. Young (7w) and mid-aged (12m) mice underwent a 15-week dietary intervention: Lean and Obese mice fed normal chow (NC) and high-fat diet (HFD) throughout, respectively. WC mice undergone HFD-induced weight gain, NC-induced weight loss, and a second HFD-induced weight regain. Late-onset obese (LO) mice ate HFD only paralleling weight regain of WC. In young, but not mid-aged mice, prior obesity accelerated weight regain upon HFD re-exposure, and aggravated glucose intolerance beyond that observed in Obese mice. This occurred without a worse adipose inflammatory profile. Rather, WC young mice exhibited blunting of light/dark-phase oscillation of feeding and energy metabolism, adipose and hepatic core clock gene oscillation, and increased hepatic expression of clock and gluconeogenic genes during the inactive phase. Restricting food availability to the active phase did not alter final weight regain, but improved glucose tolerance selectively in WC mice, normalized hepatic gluconeogenic and clock-genes expression in both liver and adipose tissue. These findings identify circadian disruption as a modifiable mediator of the adverse metabolic impact of WC in young-adulthood obesity. HighlightsO_LIWeight cycling is common in obesity, but whether it worsens metabolic dysfunction beyond persistent obesity remains unclear. C_LIO_LIWe asked whether weight cycling aggravates glucose intolerance in an age-dependent manner and whether circadian disruption contributes to this effect. C_LIO_LIIn young, but not mid-aged mice, weight cycling accelerated weight regain and worsened glucose intolerance, accompanied by blunted diurnal oscillation of behavioral parameters and core clock gene expression, without exaggerated adipose inflammation. C_LIO_LIActive-phase time-restricted feeding improved WC-induced aggravated glucose tolerance and circadian oscillation, identifying circadian disruption as a modifiable mechanism linking weight cycling adverse metabolic outcomes in young-adulthood obesity. C_LI

BackgroundVertical sleeve gastrectomy (VSG) improves glycaemic control in type 2 diabetes (T2D) through mechanisms that extend beyond weight loss. The interaction between glucocorticoid metabolism and inflammation in this context remains unclear. MethodsWe investigated the role of 11{beta}-hydroxysteroid dehydrogenase type 1 (11{beta}HSD1) in mediating the metabolic effects of VSG in humans and mice. Subcutaneous adipose tissue biopsies were collected before and 6 months after VSG. Parallel studies were conducted in lean and high-fat diet-fed mice undergoing VSG or sham surgery, alongside 11{beta}HSD1 knockout models. Glucose tolerance and expression of 11{beta}HSD1 and interleukin-6 (IL6) were assessed. Mechanistic interactions were examined in IL6-treated human hepatocytes. ResultsVSG reduced 11{beta}HSD1 and IL6 expression in human adipose tissue and improved insulin resistance. In lean mice, VSG improved glucose tolerance and downregulated both markers independently of weight loss. 11{beta}HSD1 knockout mice exhibited improved glucose tolerance despite increased adiposity, partially recapitulating the VSG phenotype. Both interventions reduced circulating and tissue IL6 levels. IL6 stimulation increased HSD11B1 expression in hepatocytes. Conclusions11{beta}HSD1 links glucocorticoid metabolism, inflammation, and glucose homeostasis following VSG. Targeting this pathway may offer a strategy to replicate key metabolic benefits of metabolic bariatric surgery.

University Students are particularly vulnerable to disordered eating behaviors (DEB) and attitudes (DEA). This study expands upon the knowledge base of DEA and DEB in university students by employing a netnography as a precursor to the main study to establish the following research questions: What is the relationship between the perceived quality of dining services and DEA? What is the relationship between the perceived availability of dining services and DEA? And lastly, how does prior experience with dining services affect eating patterns and attitudes toward food? The first study utilized a netnographic approach in order to evaluate issues with university dining services, leading to the design of the second study. Students at an upper Midwestern university (n=88) were surveyed via convenience sampling. Eating attitudes, eating behaviors, and relationships with dining services were measured. A statistically significant relationship between the availability of services and the DEA was found. A statistically significant relationship between the availability of services and risk behaviors was found. However, no statistically significant correlation existed between first-year dependence on on-campus dining services and risk behavior related to eating disorders or eating attitudes. Based on this, we know the quality of nutrition and the availability of services impacted students eating attitudes and behaviors, not inherent dependence.