Obesity

Background: Obesity has become increasingly common among US adults with hypertension. However, national data are limited on weight-loss efforts among adults with hypertension and overweight/obesity, and whether these efforts have translated into clinically meaningful weight loss at the population level. Methods: We analyzed repeated cross-sectional data from the National Health and Nutrition Examination Survey, 1999-2023. Adults aged 20 years with hypertension and body mass index 25 kg/m2 were included. Weight-loss attempt was defined as self-report of trying to lose weight during the prior 12 months. Among those attempting weight loss, successful weight loss was defined as 5% or 10% reduction in body weight over the prior year. Survey-weighted logistic regression was used to assess temporal trends and associations between strategies and successful weight loss. Results: Overall, 57.6% reported a weight-loss attempt, increasing from 55.9% in 1999-2000 to 60.4% in 2021-2023 (P for trend=0.002). The most reported strategies were eating less food (65.3%) and exercise (52.4%). Among those attempting weight loss, 33.4% achieved 5% weight loss and 14.7% achieved 10% weight loss; neither improved over time (P for trend=0.976 and 0.174, respectively). Weight-loss surgery was strongly associated with success but was rarely reported (0.35%). Eating less fat and changing eating habits were also positively associated with successful weight loss, whereas skipped meals and use of diet foods or products were inversely associated. Conclusions: Weight-loss attempts increased, but clinically meaningful weight-loss success did not improve, highlighting a persistent gap between effort and outcome in hypertension care.

Glucagon-like peptide-1 receptor (Glp1r) agonists have transformed obesity treatment, but weight loss responses to these drugs vary widely. Elucidating behavioral and metabolic phenotypes throughout Glp1r agonist treatment could identify mechanisms underlying this response spectrum. We characterized food intake, meal patterns, energy expenditure (EE), and substrate oxidation during chronic semaglutide treatment and post-treatment recovery in obese male mice at room temperature (RT) and thermoneutral temperature (TN). Semaglutide-induced weight loss and post-treatment weight regain were similar at RT and TN. Weight loss was divided into three stages at both temperatures: 1) rapid initial weight loss, 2) slower gradual weight loss, and 3) weight maintenance. Initial weight loss was marked by reduced food intake, smaller and less frequent meals, and increased lipid oxidation. Food intake gradually returned to pre-treatment levels through increased meal frequency, while meal size remained suppressed. Lipid oxidation gradually decreased while carbohydrate oxidation increased. Weight-adjusted EE and locomotor activity increased throughout semaglutide treatment. Mice rapidly regained weight after treatment cessation, and this was associated with increased food intake, meal size and frequency, carbohydrate oxidation, EE, and activity. These findings reveal that semaglutide-induced weight loss and regain after treatment cessation involve dynamic, stage-specific changes in feeding behavior, EE, and substrate oxidation. ARTICLE HIGHLIGHTSO_LIAlthough many studies demonstrate acute behavioral and metabolic effects of glucagon- like peptide-1 receptor (Glp1r) agonists, few have assessed chronic effects of these drugs on these phenotypes. C_LIO_LIWe wanted to assess changes to various behavioral and metabolic phenotypes throughout a chronic treatment regimen with semaglutide and post-treatment. C_LIO_LIWeight loss in response to chronic semaglutide treatment can be divided into distinct phases, and each phase is characterized by different effects on food intake, meal patterns, energy expenditure, and substrate oxidation. C_LIO_LIOur findings suggest that differences in behavioral changes and/or metabolic adaptations may underlie the degree of weight loss responsiveness to Glp1r agonists. C_LI

ImportanceWeight recurrence occurs in nearly 20% of patients following metabolic and bariatric surgery (MBS) and can diminish long-term metabolic benefits. While glucagon-like peptide-1 receptor agonists and gastric inhibitory polypeptide receptor agonists (GLP-1 RA) have emerged as potential adjuvant therapies, evidence supporting their use is limited primarily to liraglutide with minimal real-world data on newer agents or population-level effectiveness. ObjectiveTo evaluate the effectiveness and safety of GLP-1 RA therapy compared to non-use among patients experiencing weight recurrence following MBS. Design, Setting, and ParticipantsThis retrospective new-user cohort study utilized from the OneFlorida+ Data Trust (2015-2024) to identify adults who underwent MBS and subsequently experienced [&ge;]10% weight recurrence from nadir weight. Propensity score matching based on BMI and clinical encounter timing, combined with inverse probability of treatment weighting, was used to minimize confounding. Of 1,098 patients who underwent MBS and experienced weight recurrence, the final weighted analytic cohort included 68 GLP-1 RA users and 131 non-users at 6 months, and 72 users and 139 non-users at 12 months. ExposureInitiation of any GLP-1 RA (dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, or tirzepatide) after MBS among patients with weight recurrence. Main Outcomes and MeasuresThe primary effectiveness outcome was percentage of recurrent weight lost at 6 and 12 months. Safety outcomes included composite gastrointestinal and surgical adverse events. ResultsGLP-1 RA use was associated with significantly greater mean weight recurrence loss compared to non-use at 6 months (9.6% vs 4.3%, p = 0.005) and 12 months (14.8% vs 8.1%, p = 0.017). Among individual agents, tirzepatide was associated with the largest reductions at both 6 and 12 months (25.1% vs 5.4% and 34.4% vs 8.8%, respectively; both p < 0.001). Liraglutide demonstrated a statistically significant difference at 12 months (18.3% vs 8.4%, p = 0.004), while semaglutide and dulaglutide were not associated with statistically significant differences at either time point. No significant differences in adverse event rates were observed between groups, with composite safety outcomes occurring in 47.1% of users versus 56.5% of non-users at 6 months (HR = 1.24, 95% CI: 0.92-1.68, p > 0.05). Conclusions and RelevanceUse of GLP-1 RA for the treatment of weight recurrence following MBS represents an effective option with sustained benefits through 12 months without increased risk of adverse events. These real-world findings support adjuvant GLP-1 RA use for managing weight recurrence following MBS across diverse patient populations. Key PointsO_ST_ABSQuestionC_ST_ABSDoes the use of glucagon-like peptide-1 and gastric inhibitory polypeptide receptor agonists (GLP-1 RA) for the treatment of weight recurrence after bariatric surgery lead to significant weight loss in real-world populations? FindingsIn this cohort study of 1,098 individuals who underwent bariatric surgery and experienced weight recurrence, use of GLP-1 RA was associated with significant loss of regained weight. MeaningUse of GLP-1 RA for weight recurrence after bariatric surgery represents a viable treatment option.

ObjectiveThis study sought to determine whether the drive to regain weight following weight loss was truly long-lived in mice. MethodsWe generated a model of reduced dietary obesity (ReDO) whereby male mice with diet-induced obesity (DIO) mice were calorically restricted until weight matched to control mice, and then after a 24-hour food assessment period were pair-fed relative to control mice. We subsequently generated ReDO mice that, after CR were pair-fed relative to control mice for 0, 8, or 28 days, or chronically. Body weight, food intake, and select metabolic parameters were measured, along with whole hypothalamic Pomc gene expression. ResultsReDO mice in both experiments exhibited hyperphagia following CR, while a persistent form of hyperphagia was detected in ReDO_8d and ReDO_28d mice relative to control and chronically pair-fed mice. 4-week initial weight gain was predictive of the degree of weight regain across ReDO_8 and ReDO_28 mice. ConclusionsReDO mice exhibit a long-lived form of hyperphagia and an apparent drive to reclaim an upwardly shifted body weight set point. There was considerable variability with regard to ReDO_8 and ReDO_28 body weight regain which was correlated with the of initial degree of 4-week body-weight gain when first exposed to a high-fat diet. This study showcases the perdurance of weight loss-associated hyperphagia and introduces a prognostic tool for identifying mice that are prone towards weight regain, while setting the stage for future inquiries into the neurobiological basis of persistent hunger following weight loss owed to a dietary intervention in mice.

Preconception weight loss by metabolic-bariatric surgery (MBS) improves maternal-fetal outcomes, but little is known about its impact on offspring growth and health. The preconception bariatric surgery and child health outcomes (POSIT) study aims to estimate the effects of maternal MBS-induced preconception weight loss on infant and childhood body size, growth, and related outcomes. This report presents the methods used to construct the POSIT cohort and its baseline characteristics. This retrospective cohort study sampled members from a United States healthcare system aged 18 and older with a singleton, live birth to create three study groups: 1) a treatment group including women who underwent preconception MBS and subsequently became pregnant (n=1,374); 2) a control group matched to the MBS pre-surgery body mass index (BMI) (pre-surgery controls, n=13,740); and 3) a second control group matched to the MBS post-surgical, pre-pregnancy BMI (pre-pregnancy controls, n=13,740). MBS and pre-surgery BMI controls showed slight imbalances in that pre-surgery BMI controls were on average [~]6 months younger, had 0.6 lower BMI (44.5 kg/m2) at the time of their pregnancy and were more likely to have become pregnant in earlier years than the MBS group prior to surgery. MBS and pre-pregnancy controls had comparable age (mean {+/-} SD 33 {+/-} 5 years), pre-pregnancy BMI (33 {+/-} 6 kg/m2), and year of delivery. Following matching, the MBS group had similar socioeconomic and health disparities as the pre-surgery control group, and both were worse than pre-pregnancy control group. Pregestational maternal comorbidity index improved after MBS and matched the pre-pregnancy controls. Upon extraction of offspring growth patterns and mediation analyses of maternal weight loss and metabolic responses to MBS, study findings will investigate effects of preconception weight loss by MBS on short- and long-term child health outcomes. Results will guide future studies focusing on improving maternal preconception weight and maternal-fetal outcomes.

BackgroundPsychiatric conditions, eating disorders (EDs), and exposure to violence are highly prevalent in patients with severe obesity. However, their association with postoperative weight trajectories following bariatric surgery remains unclear. ObjectiveTo assess the associations between eating disorders, psychiatric conditions, and history of violence with multiple dimensions of weight trajectory after bariatric surgery. MethodsThis retrospective study included 414 patients with severe obesity from the OBESEPI cohort who underwent bariatric surgery at Nancy University Hospital (France). Psychological factors were assessed using a standardized preoperative psychiatric interview. Weight outcomes included preoperative BMI change, maximal BMI loss ({Delta}BMImax), final BMI change (dBMIdf), weight regain (BMIR), and magnitude of weight regain (dBMIR). Multivariable linear and logistic regression models were adjusted for age and sex. ResultsPsychological factors were not associated with baseline BMI or preoperative BMI variation. A history of violence was significantly associated with greater maximal BMI loss ({beta} = 1.99, 95% CI [0.73-3.26]; p = 0.002) and greater final BMI reduction ({beta} = 1.81, 95% CI [0.47- 3.14]; p = 0.009). Eating disorders and psychiatric conditions were not associated with weight loss outcomes. No association was observed between overall exposure to violence and weight regain. However, subtype analyses showed that physical violence was associated with a higher risk of weight regain, whereas psychological violence was associated with a lower risk. No significant associations were found for the magnitude of weight regain. ConclusionsEating disorders and psychiatric conditions were not associated with postoperative weight outcomes in this cohort. In contrast, exposure to violence--particularly when differentiated by subtype--was associated with distinct patterns of weight loss and regain. These findings highlight the relevance of trauma-informed assessment in bariatric care and support a more individualized approach to obesity management.

BackgroundMaternal prepregnancy body mass index (BMI) is a critical determinant of pregnancy outcomes, influencing risks for gestational diabetes, hypertensive disorders, cesarean delivery, stillbirth, and long-term maternal and child health. Although the overall rise in obesity among reproductive-aged women in the United States is well recognized, recent national data describing detailed trends by race and ethnicity are limited. ObjectiveTo examine temporal trends in prepregnancy BMI among U.S. mothers from 2016 to 2023, with a focus on changes in normal weight and obesity prevalence across racial and ethnic groups. MethodsWe performed a retrospective analysis of nearly 30 million live births recorded in the CDC Natality database. Maternal BMI was categorized as underweight, normal weight, overweight, and obesity classes I-III. Race and ethnicity were defined using CDC conventions: non-Hispanic (NH) White, NH Black, NH Asian, NH American Indian or Alaska Native, NH Native Hawaiian or Pacific Islander, NH more than one race, and Hispanic (all races). Annual prevalence for each BMI category was calculated, and linear regression was used to estimate slopes of annual change with 95% confidence intervals. ResultsNationally, normal weight prevalence declined from 42% in 2016 to 37% in 2023, while combined obesity increased from 24% to 29%. Declines in normal weight and corresponding increases in obesity were observed across all racial and ethnic groups. Asian mothers had the highest prevalence of normal weight (60% in 2016, 53% in 2023) and the lowest obesity prevalence (<15%), yet still showed significant annual increases. By 2023, obesity prevalence exceeded 30% among Black and American Indian/Alaska Native mothers and reached 25-30% among Hispanic and multiracial mothers. Hispanic and Black mothers experienced the steepest annual increases in obesity (+0.98% and +0.93% per year, respectively). Projections indicate that normal weight prevalence could fall below 30% within the next decade, while obesity prevalence may approach 40% by the mid-2030s. ConclusionsBetween 2016 and 2023, U.S. mothers experienced a population-wide redistribution from normal weight to obesity, affecting all racial and ethnic groups. These trends pose substantial risks for adverse pregnancy outcomes and threaten to exacerbate maternal health inequities. Equity-focused preconception counseling, nutrition education, and policy-level interventions are urgently needed.

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 ([&ge;]18 years); and date (pregnancy onset date in 2006-2020, delivery [&le;]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.

BackgroundIndividual weight loss response to the GLP-1 receptor agonist semaglutide varies considerably, with many possible contributing factors. Leveraging multiple clinico-genomic cohorts, we analyzed differences in weight loss trajectories according to patient characteristics, including a polygenic score (PGS) and metabolic risk factors, in semaglutide initiators with BMI [&ge;]27 kg/m2. MethodsThis longitudinal study utilized clinical-grade exome sequencing and electronic health record data from six U.S. cohorts within the Helix Research Network (n=134,806). A BMI PGS was calculated using 26,941 variants. Twelve-month weight loss trajectories were modeled using mixed effects models, and associations with demographics, PGS, comorbidities, medications, and laboratory results were evaluated. FindingsAmong 1,923 semaglutide users, the mean pretreatment BMI was 38.4 kg/m2. For those on doses [&ge;]1.7 mg, the mean body weight reduction was 7.3% at 6 months and 9.9% at 12 months. Over 12 months, low PGS was associated with an adjusted 1.5% and 1.8% additional weight loss compared to intermediate and high PGS, respectively (both p<0.01). Male sex, type 2 diabetes, hypertension, obstructive sleep apnea, and non-alcoholic fatty liver disease were each associated with 1.2%-1.9% less weight loss (all p<0.05). In type 2 diabetes, each 1%-increase in pretreatment hemoglobin A1c was associated with 0.6% less weight loss (p=0.0019). InterpretationAmong adults with overweight or obesity, a lower genetic predisposition to obesity is linked to greater weight loss on semaglutide. Additionally, metabolic health significantly impacts the drugs effectiveness. These findings underscore the importance of precision medicine in obesity management. FundingRenown Health Foundation. Nevada Governors Office of Economic Development. HealthPartners.

Background & AimsWeight loss is associated with an improvement of insulin sensitivity. Both, a negative energy balance and changes of body composition are integrative components of weight loss interventions. However, the individual impact of these two components on insulin sensitivity and energy metabolism is unclear. MethodsWe performed a randomized controlled trial including 80 overweight or obese post-menopausal women. Participants randomly assigned to the intervention group underwent an 800 kcal/d liquid diet for 2 months followed by four weeks in which the formula diet was substituted by a calorie reduced healthy diet to facilitate further weight loss. This weight loss phase was followed by a 4-week weight maintenance phase, where weight stability was achieved by individualized daily caloric intake without negative energy balance. Volunteers of the control group were instructed to keep their weight stable during the entire period of 4 months. Metabolic phenotyping was performed in both groups at baseline (M0), after weight loss (M3) and after the maintenance period (M4). Additional phenotyping was performed during follow-up at 12 (M12) and 24 months (M24). Primary outcomes were changes of lean body mass (LBM) and changes of insulin sensitivity (ISIClamp) between baseline and M3 and M4. Estimates of energy metabolism were secondary endpoints. ResultsNo significant changes of body weight or LBM were found in the control group between any time points. A significant reduction of body weight, fat mass (FM) and LBM was found in the intervention group between M0 and M3, while no further change was seen between M3 and M4. Only subjects of the intervention group were characterized by an improvement of the second primary outcome ISIClamp at M3, which was preserved until M4. Notably, a lower resting energy expenditure per LBM (REELBM) at M3 as well as the individual difference of REELBM between M3 and M4 significantly predicted a stronger regain of fat mass during follow-up. ConclusionsIn summary, our data demonstrate that modulation of LBM and insulin sensitivity during weight loss is predominantly driven by changes in body weight and body composition, rather than an individual effect of negative energy balance. However, the variance in energy expenditure during negative and steady energy balance indicates a thrifty phenotype, which is highly susceptible to future regain of fat mass.

ObjectiveCold exposure is one of the most powerful physiological stimuli for thermogenic adipose tissue activity and may positively impact metabolic homeostasis. An important gap in knowledge is whether mice with diet-induced obesity respond to cold similarly to their lean counterparts. The goal of the present study was to compare the response to cold exposure between mice fed a standard (normal-fat) diet and a higher-fat diet. MethodsMale C56BL/6J mice fed a standard diet (13.1% fat) or a higher-fat diet (21.6% fat) during adulthood and exposed to cold (4-6{degrees}C) following different approaches. Body weight, body composition, food intake, rectal temperature, energy expenditure, and respiratory exchange ratio were assessed. ResultsCold exposure significantly increased energy expenditure and limited weight gain despite elevated food intake in mice fed either a standard or a higher-fat diet, while body composition, body temperature, and respiratory exchange ratio remained stable across both dietary groups. Moreover, energy expenditure measured at 4-6 {degrees}C was comparable between mice fed standard and higher-fat diets, demonstrating that cold-induced thermogenesis may elicit a consistent metabolic response independent of dietary fat content. ConclusionsOur results demonstrated that cold exposure increased energy expenditure in both lean and obese animals, highlighting thermogenesis as a promising target for obesity treatment beyond current approaches focusing on appetite suppression. HighlightsO_LICold exposure increases energy expenditure and limits weight gain in both control diet and higher-fat diet-fed mice, despite increased food intake. C_LIO_LICore body temperature and body composition remain stable during cold exposure, regardless of dietary fat content. C_LIO_LICold-induced thermogenesis elicits a comparable metabolic response in control diet and higher-fat diet-fed mice, supporting its potential as a therapeutic strategy for obesity. C_LI

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.

BackgroudThis study aimed to assess the effects of a 16-week supervised exercise intervention on ovarian function in women undergoing bariatric surgery (BS); and to examine potential mechanisms associated with the changes in ovarian function. Materials and MethodsA randomized, two-arm parallel-group trial was conducted from October 2019 to September 2022. Participants were reproductive-aged women with severe obesity (BMI [&ge;]40 kg/m2 or BMI [&ge;]35 with comorbidities) recruited from the BS services from two hospitals. Participants were randomly assigned to BS+usual care (n = 25) or BS+exercise (n = 21), consisting of 16 weeks of three-weekly supervised exercise sessions. Outcomes were assessed before surgery, at week 16, and 1-year. The primary outcome was the change in sex-hormone binging globulin (SHBG). Secondary outcomes were related to ovarian function (obtained from both serum and transvaginal ultrasound), weight loss, body composition, fitness, inflammation, cardiometabolic and nuclear magnetic resonance-derived metabolomic profiles. ResultsA total of 42 participants (91%; 18 in BS+EX; 24 in BS+usual care) were included in the primary analyses. There were no between-group differences at week 16. At 1-year, the exercise group increased serum SHBG levels (+36.3 nmol/L; 95%CI 2.3 to 70.2; p=0.037), oocyte count (+3.1 follicles; 95%CI 0.9 to 5.3; p=0.007), and reduced the uterine artery mean pulsatility index (UtA-PI) (-1.3; 95%CI -2.1 to -0.5; p=0.003) compared to usual care, despite comparable weight loss and changes in secondary/exploratory outcomes. The 1-year changes in metabolomic profile predicted 97% of the increase in SHBG in the exercise group. Interestingly, the decrease in serum amino acid levels was associated with increased SHBG levels at 1-year, only in the exercise group. Sensitivity analyses corroborated the results. ConclusionThe EMOVAR trial suggests that a 16-week supervised exercise program improves relevant markers of ovarian function, such as SHBG, oocyte count, and UtA-PI, at 1-year compared to usual care.

To curb the obesity epidemic, it is imperative that we improve our understanding of the mechanisms controlling fat mass and body weight regulation. While great progress has been made in mapping the biological feedback forces opposing weight loss, the mechanisms countering weight gain remain less well defined. Here, we integrate a mouse model of intragastric overfeeding with a comprehensive evaluation of the regulatory aspects of energy balance, encompassing food intake, energy expenditure, and fecal energy excretion. To evaluate the role of adipose tissue thermogenesis in the homeostatic protection against overfeeding-induced weight gain, we exposed uncoupling protein 1 (UCP1) knockout (KO) mice to overfeeding. Our results confirm that 7 days of 150% overfeeding induces [~]11% weight gain and triggers a potent and prolonged reduction in voluntary food intake that drives body weight back to baseline following overfeeding. Overfeeding has no effects on energy expenditure, consistent with the observation that mice lacking UCP1 are not compromised in their ability to defend against overfeeding-induced weight gain. These data emphasize that whole-body energy expenditure and adipose thermogenesis are not key contributors to protection against overfeeding in mice. Lastly, we show that fecal energy excretion decreases in response to overfeeding, primarily driven by a reduction in fecal output rather than in fecal caloric content. In conclusion, these results challenge the prevailing notion that adaptive thermogenesis contributes to the defense against weight gain induced by overfeeding. Instead, the protection against enforced weight gain in mice is primarily linked to a profound reduction in food intake.

BackgroundCachexia is a multifactorial syndrome of involuntary weight loss, skeletal muscle wasting, and metabolic dysregulation, commonly seen in advanced cancer and other chronic diseases. Despite its prevalence and prognostic significance, effective treatment strategies remain limited, and there is no standardized model of outpatient care in the US. ObjectiveTo describe the structure, patient characteristics, and outcomes of a multidisciplinary cancer cachexia clinic embedded within an academic endocrinology practice. MethodsWe conducted a retrospective analysis of 103 patients referred to a single-center cachexia clinic over five years. Patients underwent comprehensive assessments including weight trajectory, nutritional status, physical performance (5x sit-to-stand test, handgrip strength), and received individualized interventions involving nutrition counseling, resistance training, and pharmacologic management. ResultsThe median patient age was 69.7 years, with 64.1% having a cancer diagnosis (61.0% with metastases). Median monthly weight loss decreased from -0.5 kg/month in the 6 months pre-enrollment to 0.0 kg/month after 3 months post enrollment (p < 0.0001), indicating significant stabilization. The 5x sit-to-stand test improved (p = 0.022), though handgrip strength remained unchanged. Patients prescribed an exercise video program trended toward greater weight gain ({beta} = +1.988, p = 0.079), while those prescribed protein powder tended to experience more weight loss ({beta} = -2.102, p = 0.113), although this difference was not statistically significant. ConclusionA multimodal cachexia clinic can stabilize weight loss and improve physical function in medically complex patients. These findings support the integration of interdisciplinary approaches to cachexia management and provide a framework for evaluating future interventions in routine clinical settings.

ImportanceUnderserved pregnant individuals experience the highest risk of aberrant pregnancy weight gain and adverse perinatal outcomes. The Women, Infants, and Children (WIC) federal program assists underserved pregnant individuals and is therefore positioned to offer equitable access to interventions to enhance gestational weight gain in accordance with clinical guidelines. ObjectiveTest effectiveness of a pragmatic, fully remote lifestyle intervention co-developed with WIC participants on the incidence of gestational weight gain guideline attainment and perinatal outcomes. DesignThe SmartMoms in WIC trial was a single-blind randomized clinical trial conducted from July 2019 to May 2024. SettingLouisiana WIC Program pregnant participants across 31 participating WIC clinics. Participants1300 individuals were recruited from Louisiana WIC; 756 were excluded via phone call and 544 were screened in person; 351 were enrolled. Randomization was stratified by geographical region and BMI class. InterventionA high intensity multicomponent e-health intervention ("Healthy Beginnings") for gestational weight gain management or usual care between 10 to 16 weeks gestation and until delivery ([~]24 weeks). Main Outcome(s) and Measure(s)The primary outcome was assessed at participants WIC clinic and included gestational weight gain guideline attainment with total observed weight gain, weight gain per week and deviation from guidelines as secondary outcomes. Perinatal outcomes from birth certificates were exploratory. ResultsThe study sample (179 Intervention; 172 Usual Care) was diverse: 39% with obesity; 57% non-Hispanic Black. The incidence of guideline attainment was not different between groups. Study observed total (adjusted mean difference, -1.4 kg; 95% CI, -2.8 to -0.1), and rate of weight gain (adjusted mean difference -0.07 kg/wk; 95% CI, -0.13 to -0.01) and the deviation from guidelines was lower in the Intervention Group compared to Usual Care. There were 43 cases (16/172 Intervention, 27/171 Usual Care) of preterm birth and 30 NICU admissions (12/172 Intervention, 18/171 Usual Care) equating to an adjusted relative risk reduction of 36.9% and 28.6%, respectively. Conclusions and RelevanceA fully remote lifestyle intervention concomitant with WIC clinical care lowered gestational weight gain and reduced the risk of preterm birth and NICU admission. Trial RegistrationClinicalTrials.gov NCT04028843 ABSTRACTO_ST_ABSBackgroundC_ST_ABSUnderserved pregnant individuals experience the highest risk for weight gain outside clinical guidelines and adverse perinatal outcomes. The Women, Infants, and Children (WIC) federal program assists underserved pregnant individuals with supplemental nutrition. WIC is positioned to offer equitable access to interventions promoting recommended gestational weight gain, complementing clinical care. MethodsIn a state-wide randomized controlled trial, pregnant WIC participants were randomly assigned to a co-developed multicomponent e-health intervention for gestational weight gain management or usual care between 10 to 16 weeks gestation. The primary outcome was gestational weight gain guideline attainment. Study observed weight gain, weight gain per week and deviation from guidelines were secondary outcomes. Perinatal outcomes from birth certificates were exploratory. ResultsPregnant participants (n=351) were enrolled (179 Intervention; 172 Usual Care) across 31 WIC clinics. The study sample was diverse: 39% with obesity; 57% non-Hispanic Black. The incidence of guideline attainment was not different between groups. Study observed weight gain (adjusted mean difference, -1.4 kg; 95% CI, -2.8 to -0.1), rate (adjusted mean difference, -0.07 kg/wk; 95% CI, -0.13 to -0.01) and the deviation from guidelines was lower in the Intervention Group compared to Usual Care. There were 43 cases (16/172 Intervention, 27/171 Usual Care) of preterm birth and 30 NICU admissions (12/172 Intervention, 18/171 Usual Care) equating to an adjusted relative risk reduction of 36.9% and 28.6%, respectively. ConclusionA fully remote lifestyle intervention concomitant with WIC clinical care lowered gestational weight gain and reduced the risk of preterm birth and NICU admission. Trial registrationClinicalTrials.gov NCT04028843 Key PointsO_ST_ABSQuestionC_ST_ABSCan a pragmatic, fully remote lifestyle intervention improve gestational weight gain and perinatal outcomes in underserved pregnant WIC participants? FindingsIn this state-wide randomized controlled trial that included 351 pregnant WIC participants, the incidence of National Academy of Medicine guideline attainment for weight gain did not differ. Study observed gestational weight gain, preterm birth, and NICU admissions were lower in the Intervention Group. MeaningA fully remote lifestyle intervention concomitant with WIC clinical care attenuated gestational weight gain and improved perinatal outcomes.

BackgroundIn pregnancy, epidemiological data have consistently shown strong associations between sleep quality and duration and maternal glycemia. However, other sleep disturbances such as difficulty falling asleep and staying asleep are common in pregnancy. They may contribute to impaired maternal glycemia through sympathetic nervous system activity, systemic inflammation, and hormonal pathways. However, there is little research examining associations between these specific sleep disturbances and maternal glycemia. ObjectiveThis study aimed to investigate the associations of sleep disturbances during mid-pregnancy and mid-pregnancy maternal glycemia and gestational diabetes subtypes. Study DesignThis is a secondary data analysis of the Comparison of Two Screening Strategies for Gestational Diabetes trial. Participants (n = 828) self-reported the frequency of sleep disturbances (i.e., trouble falling asleep, trouble staying asleep, waking several times per night, and waking feeling tired or worn out) in mid-pregnancy. Gestational diabetes was diagnosed using either the International Associations of Diabetes and Pregnancy Study Groups or Carpenter-Coustan approach. We defined gestational diabetes subtypes based on the degree of insulin resistance and beta-cell dysfunction. We used multinomial logistic regression to examine associations of sleep disturbances with gestational diabetes status (i.e., normal, mild glycemic dysfunction, and gestational diabetes) and gestational diabetes subtypes (i.e., neither insulin resistance or beta-cell dysfunction, insulin resistance only, beta-cell dysfunction only, and insulin resistance and beta- cell dysfunction). ResultsA total of 665 participants (80%) had normal glycemia, 81 (10%) mild hyperglycemia, and 80 (10%) had gestational diabetes. Among participants with gestational diabetes, 62 (78%) had both insulin resistance and beta-cell dysfunction, 15 (19 %) had insulin resistance only, and 3 had beta-cell dysfunction only or neither insulin resistance nor beta-cell dysfunction. Sleep disturbance frequency was not associated with maternal glycemia or gestational diabetes subtypes. ConclusionsSleep disturbances in mid-pregnancy were not associated with maternal glycemia during mid-pregnancy. Future research should collect data on sleep disturbances at multiple time points in pregnancy and in combination with other sleep disturbances to determine whether sleep plays any role in maternal glycemic control.

BackgroundLarge for gestational age birth weight is associated with both short- and long-term health consequences for offspring, and fetal genetics may contribute to risk for large for gestational age birth weight. ObjectivesWe evaluated the relationship between a polygenic growth score and the risk for large gestational age birth weight. We also delineated the between the polygenic growth score and risk for large for gestational age birth weight in relation to maternal glycemia and body mass index, both of which are established risk factors for large for gestational age birth weight. Study designThis is a secondary analysis of a prospective multicenter cohort study in which nulliparous individuals were recruited from eight clinical sites in the United States. A subset of infants (n=3865) with DNA available were genotyped, and a previously developed polygenic growth score for large for gestational age birth weight was calculated. We evaluated the relationship between tertiles of the polygenic growth score, maternal body mass index, and glycemia assessed by the 50-gram glucose challenge test on the risk for large for gestational age birth weight using one-way ANOVA and Chi-squared tests as well as a regularized linear model. ResultsOf the 3,865 individuals with infant genotype available, 3,286 (84.9%) were included in this analysis. A polygenic growth score in the first tertile was associated with a lower risk for large for gestational age (OR 0.71, 95% CI 0.53-0.94), while a polygenic growth score in the third tertile was associated with a higher risk for large for gestational age birth weight (OR 1.29, 95% CI 1.02-1.63). Maternal body mass index was more strongly associated with the risk for large for gestational birth weight than maternal glycemia. The odds of large for gestational age birth weight were significantly higher with a maternal body mass index [&ge;]35 kg/m2 and a PGS of either the second tertile (OR 3.54, 95% CI 1.96-6.38) or third tertile (OR 2.69, 95% CI 1.54-4.71). ConclusionsThe polygenic growth score has a modest ability to identify fetuses at higher or lower risk for Large for gestational age birth weight in a multiracial cohort from the United States. Polygenic growth score could assist with identification of those fetuses at increased risk for LGA birth weight among individuals with a BMI [&ge;]35 kg/m2, which may allow for targeted interventions such as dietary and lifestyle modifications to optimize the in-utero environment.

ObjectiveBMI alone does not capture obesity-related health heterogeneity. The Edmonton Obesity Staging System (EOSS) grades obesity severity based on comorbidities and functional impairment, whereas the Lancet Commission Diagnostic Model for Obesity (DMO) distinguishes preclinical from clinical obesity based on organ dysfunction. We assessed whether both frameworks identify overlapping phenotypes and how they classify obesity severity. MethodsA modified EOSS and DMO were applied to the UK Biobank (N {approx} 411,000). Stage distributions, cross-classification, and the impact of combining BMI with fat distribution on obesity categorization were analyzed. ResultsAbout one quarter of participants were classified with obesity under both frameworks. Most were assigned to advanced stages, with high concordance for established disease. Differences were most pronounced in early stages: DMO captured a broader spectrum of mild/subclinical organ dysfunction, whereas EOSS emphasized established disease with prognostic relevance. Discrepancies reflected differences in operationalization of e.g. metabolic, cardiovascular, and mental health. Obesity thresholds influenced classification, with [~]50% reclassified when BMI was combined with different fat distribution parameters, highlighting sensitivity of early-stage assignment. ConclusionEOSS and DMO provide complementary perspectives on obesity severity. Integrating EOSSs prognostic granularity with DMOs multidimensional approach may improve risk stratification and identify individuals most suitable for intensive interventions. STUDY IMPORTANCEO_ST_ABSWhat is already known?C_ST_ABSO_LIBMI alone poorly reflects obesity-related health risk; comorbidities, organ dysfunction, and functional impairments are crucial for precise staging. C_LIO_LITwo major frameworks exist: EOSS focuses on prognostic severity, while DMO identifies early/preclinical obesity--but their agreement and clinical implications were unclear. C_LI What does this study add?O_LIDemonstrates that EOSS emphasizes established disease and prognostic severity, whereas DMO captures a broader spectrum of early or subclinical organ dysfunction, revealing distinct phenotypes within the same BMI-defined population. C_LIO_LIHighlights that combining BMI with anthropometric measures can reclassify up to [~]50% of individuals, illustrating the sensitivity of early-stage assignment to diagnostic thresholds. C_LI How might these results change the direction of research or the focus of clinical practice?O_LIIntegrating EOSSs prognostic detail with DMOs broad, multidimensional approach enables targeted intervention, helping clinicians prioritize patients for intensive obesity management or treatment. C_LIO_LIProvides evidence for harmonizing obesity classification beyond BMI, emphasizing the need for multidimensional assessment in both research cohorts and routine clinical practice. C_LI

BackgroundPostoperative outcomes vary considerably across bariatric patients and may be related to psychosocial factors. In this study, we examined whether a patients family support predicts weight loss and the remission of type 2 diabetes (T2DM) up to 5 years following surgery. MethodsBetween 2008 to 2018, 359 patients completed a pre-surgical questionnaire before undergoing gastric bypass or sleeve gastrectomy. As part of the questionnaire, patients described their family support in terms of structure (marital status, number of family members in the household) and function (marriage satisfaction, family emotional support, family practical support). These were applied as predictors to percent total weight loss (%TWL) and T2DM remission at 1, 2, 3, 4, and 5 years following surgery. ResultsMarital satisfaction was found to be a significant predictor of post-surgical weight trajectories. Namely, patients who reported higher marital satisfaction were more likely to sustain weight loss than patients who reported lower marital satisfaction ({beta} = 0.92, SE = 0.37, p = 0.02). ConclusionsGiven the link between marital support and long-term weight outcomes, providers could consider asking patients about their spousal relationships during pre-surgical counselling. Key Points Psychosocial factors may influence postoperative outcomes Family support was examined as a predictor of weight loss and type 2 diabetes Marital satisfaction significantly predicted post-surgical weight trajectories