International Journal of Obesity最新文献

{"title":"Utilization and outcomes of nutrient-stimulated hormone therapies in patients undergoing bariatric surgery.","authors":"Claudia R Villatoro Santos, Hector D Estrada Tock, Haoran Tang, Laura N McEwen, Andrew Kraftson, William H Herman, Amy E Rothberg","doi":"10.1038/s41366-026-02159-3","DOIUrl":"https://doi.org/10.1038/s41366-026-02159-3","url":null,"abstract":"<p><strong>Objective: </strong>To describe the impact of nutrient-stimulated hormone (NuSH) therapies on weight loss by bariatric surgery type, diabetes status, and timing of initial NuSH prescription.</p><p><strong>Methods: </strong>Retrospective study of 1638 adults who underwent bariatric surgery at a single academic medical center between 2015 and 2022. Baseline demographics, NuSH therapy prescriptions, and follow-up weights were obtained from electronic health records. We calculated percent total weight loss (%TWL) over time using linear mixed models.</p><p><strong>Results: </strong>Patients who underwent Roux-en-Y gastric bypass (RYGB) had greater %TWL compared to those who underwent sleeve gastrectomy (SG). Those without diabetes had greater %TWL compared to those with diabetes. At 72 months, adjusted average %TWL was highest in patients who received NuSH prescriptions both before and after surgery (22.7%, 95% CI: 17.9-27.5), followed by those with prescriptions only after surgery (19.9%, 95% CI: 18.3-21.4) and those without prescriptions (19.6%, 95% CI: 18.1-21.2). The greatest %TWL was seen in patients who had prescriptions within 6 months after surgery.</p><p><strong>Conclusion: </strong>Individuals who underwent RYGB and who did not have diabetes had the highest %TWL. Receiving a NuSH prescription both before and after surgery and early NuSH initiation were associated with the greatest %TWL.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum biophysical platform for deterministic satiety signaling modulation and metabolic homeostasis in human cohorts.","authors":"Sitthipon Somsai","doi":"10.1038/s41366-026-02137-9","DOIUrl":"https://doi.org/10.1038/s41366-026-02137-9","url":null,"abstract":"<p><p>Current translational approaches to obesity and metabolic syndrome predominantly rely on chemical interventions modeled via stochastic passive diffusion. These traditional methods inherently lack spatial targeting and temporal precision, often resulting in delayed therapeutic onset. Here, we present a paradigm shift using a novel quantum biophysical framework that treats the gastrointestinal microenvironment as a non-equilibrium semiconductor network. By engineering a Metabolite Conjugate Prebiotic (MCP) platform with an embedded polyphenolic tannin matrix, we command targeted electron translocation across microbial membranes, establishing a directional \"metabolic pull.\" Validated against a Real-World Evidence (RWE) cohort of 2,000 subjects, this platform demonstrated an accelerated biological response window, achieving rapid and deterministic activation of satiety signaling within 15 to 60 min. Notably, while the FDA recommends 20 to 25 grams per day for traditional prebiotics, participants in this cohort required a significantly minimized dosage of only 2 to 3 grams of MCP per day to elicit these homeostatic effects. The computational framework yields a 92 percent clinical predictive accuracy, significantly outperforming classical stochastic models. This platform offers a scalable, highly predictable avenue for precision translational medicine in metabolic health.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toddler diet quality: a factor associated with childhood growth?","authors":"Xuanxuan Zhu, Diane L Putnick, Priscilla K Clayton, Tzu-Chun Lin, Edwina Yeung","doi":"10.1038/s41366-026-02169-1","DOIUrl":"https://doi.org/10.1038/s41366-026-02169-1","url":null,"abstract":"<p><strong>Background: </strong>Childhood growth is crucial for long-term overall health and well-being. Diet quality is an essential component of nutritional status reflecting dietary patterns and nutrient intake. While research in adults has shown that higher diet quality is associated with a lower risk of obesity, its association with childhood growth has remained unclear. This study aims to evaluate the association between diet quality among toddlers and their growth in later childhood.</p><p><strong>Methods: </strong>Mothers from Upstate KIDS, a prospective cohort study, reported numbers of servings/day for specific foods, such as dairy, fruit, vegetables, and meat, fed to their toddlers at 2.5- and 3-years along with behaviors such as breakfast intake. Accordingly, the Youth Healthy Eating Index (YHEI) was calculated to measure toddler diet quality (range 0-65) with higher scores indicating better toddler diet quality. Children's height, weight, and waist circumference were reported up to three times in questionnaires from 7- to 9-years, and corresponding height-for-age (HAZ), weight-for-age (WAZ), body mass index-for-age (BMIZ) z-scores and obesity status were calculated. Mixed effects models were used to estimate associations with YHEI scaled per five-unit increase, adjusting for maternal age, race/ethnicity, education, insurance status, government assistance, fertility treatment, smoking, parity, pre-pregnancy BMI, child age, sex, plurality, breastfeeding duration, and complementary feeding.</p><p><strong>Results: </strong>Among 1322 children (52.0% male), the mean YHEI score in toddlerhood was 44.4 <math><mo>±</mo></math> 8.52 (mean  <math><mrow><mo>±</mo> <mspace></mspace></mrow> </math> standard deviation). Higher YHEI scores were significantly associated with lower odds of developing central obesity (adjusted OR = 0.74, 95% CI: 0.56, 0.98). YHEI scores were not associated with HAZ, WAZ, BMIZ, waist circumference, and obesity after adjusting for covariates.</p><p><strong>Conclusion: </strong>Higher toddler diet quality is associated with reduced odds of central obesity in later childhood. Interventions aimed at improving early diet quality are needed to promote healthy growth in childhood.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adopting the lancet commission definition of clinical obesity in metabolic dysfunction-associated steatotic liver disease (MASLD).","authors":"Karen Cheuk-Ying Ho, Rex Wan-Hin Hui, Trevor Kwan-Hung Wu, Chi-Ho Lee, David Tak-Wai Lui, Man-Fung Yuen, Wai-Kay Seto, Lung-Yi Mak","doi":"10.1038/s41366-026-02173-5","DOIUrl":"https://doi.org/10.1038/s41366-026-02173-5","url":null,"abstract":"<p><strong>Background: </strong>The Lancet Diabetes & Endocrinology Commission proposed a new definition of clinical obesity. We applied clinical obesity in a cohort of Asian patients with metabolic dysfunction-associated steatotic liver disease (MASLD) to evaluate its associations with clinical outcomes.</p><p><strong>Methods: </strong>We enrolled 642 MASLD patients with vibration-controlled transient elastography (VCTE) assessment. A subgroup of 254 patients underwent additional bioelectrical impedance analysis (BIA). The diagnosis of clinical obesity required fulfilment of both anthropometric and clinical criteria. At-risk metabolic dysfunction-associated steatohepatitis (MASH) was defined by FibroScan-AST (FAST) score. Major adverse cardiovascular events (MACE) were defined as a composite outcome of acute coronary syndrome or stroke.</p><p><strong>Results: </strong>Among 642 MASLD patients (mean age 55.8 ± 12.5 years; 49.2% male, mean BMI 28.2 ± 4.7 kg/m², 76% severe steatosis, 12.5% advanced fibrosis/cirrhosis [F3/F4]), 46.1% of patients fulfilled the diagnosis of clinical obesity. Clinical obesity criteria identified more patients with F3/F4 (20.6% vs 8.1%, p < 0.001), severe steatosis (83.8% vs 67.6%, p < 0.001), at-risk MASH (3.4% vs 0%, p = 0.056) and MACE (11.2% vs 2.7%, p = 0.006) compared with BMI-based criteria. Clinical obesity was an independent predictor of F3/F4 (OR 4.074, 95% CI 2.195-7.563, p < 0.001) and severe steatosis (OR 2.441, 95% CI 1.638-3.637, p < 0.001). Among patients with BIA, clinical obesity was associated with a lower appendicular skeletal muscle mass (27.0% vs 41.1%, P < 0.001) and a greater visceral fat index (15 vs 9, p < 0.001) compared with BMI-based criteria.</p><p><strong>Conclusion: </strong>Clinical obesity criteria identified more MASLD patients with F3/F4, severe steatosis, at-risk MASH and MACE compared with BMI-based obesity criteria. It should be regularly utilized for prognostication in MASLD evaluation.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleeve gastrectomy induces adipose browning via suppression of Asprosin and activation of the ATF3-Nrf2/HO-1 axis.","authors":"Shuai Zhao, Yayan Fu, Ziwei Ding, Mengli Zi, Jie Wang, Jiajie Zhou, Ruiqi Li, Wei Wang, Daorong Wang","doi":"10.1038/s41366-026-02167-3","DOIUrl":"https://doi.org/10.1038/s41366-026-02167-3","url":null,"abstract":"<p><strong>Background: </strong>Vertical sleeve gastrectomy (VSG) produces rapid metabolic improvement in obesity and type 2 diabetes mellitus (T2DM), yet the molecular basis linking surgery to adipose remodeling remains unclear. The fasting-induced adipokine Asprosin is implicated in metabolic dysregulation, but its role in white adipose tissue (WAT) browning after VSG is unknown.</p><p><strong>Methods: </strong>Asprosin expression was assessed in human adipose tissues and longitudinally after VSG. A high-fat diet/streptozotocin-induced rat model with obesity and diabetes and differentiated 3T3-L1 adipocytes were used for in vivo and in vitro mechanistic studies, including AAV-mediated knockdown, pharmacological inhibition, CUT&Tag, and luciferase assays.</p><p><strong>Results: </strong>Asprosin was elevated in obesity and reduced after VSG. In rats, VSG improved metabolic parameters and promoted WAT browning, accompanied by suppression of Asprosin and activation of ATF3-Nrf2/HO-1 signaling. Mechanistically, ATF3 was associated with increased Nrf2 promoter activity and appears to contribute to Asprosin-dependent regulation of thermogenic gene expression. Asprosin knockdown enhanced VSG-induced browning in a HO-1-dependent manner. These findings suggest a potential link between Asprosin suppression and activation of the ATF3-Nrf2/HO-1 axis during VSG-induced adipose browning.</p><p><strong>Conclusions: </strong>VSG is associated with WAT browning, which may involve suppression of Asprosin and activation of the ATF3-Nrf2/HO-1 axis, providing mechanistic insight into metabolic improvement after bariatric surgery.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT07008274.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking cardiometabolic therapy thresholds in individuals with obesity.","authors":"Shaun Khanna, Nitesh Nerlekar, Aditya Bhat","doi":"10.1038/s41366-026-02160-w","DOIUrl":"https://doi.org/10.1038/s41366-026-02160-w","url":null,"abstract":"","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early signs of nephropathy in adolescents with obesity.","authors":"Maksymilian Sikorski, Krzysztof Skoczyński, Kacper Mitoraj, Jakub Pilip, Michał Pac, Sebastian Więckowski, Joanna Fornalska, Maciej Jaworski, Agnieszka Kolczyńska-Pędich, Katarzyna Skoczek, Anna Świąder-Leśniak, Małgorzata Wajda-Cuszlag, Łukasz Obrycki, Mieczysław Litwin","doi":"10.1038/s41366-026-02175-3","DOIUrl":"https://doi.org/10.1038/s41366-026-02175-3","url":null,"abstract":"<p><strong>Background: </strong>Childhood obesity is increasingly recognized as a risk factor for chronic kidney disease; however, early structural and functional kidney alterations remain incompletely characterized.</p><p><strong>Methods: </strong>We conducted a cross-sectional study including 768 adolescents with obesity aged 10-18 years. Kidney function (KF) was assessed using creatinine-/cystatin C-based estimated glomerular filtration rate (eGFR), along with urinary albumin- and protein-to-creatinine ratio (ACR, PCR). Kidney length (KL) and volume (KV) were measured by ultrasound and expressed as standard deviation scores (SDS) using reference values.</p><p><strong>Results: </strong>Increasing BMI-SDS was associated with lower GFR estimates: creatinine-based eGFR across BMI-SDS categories from 112 to 105 ml/min/1.73 m², cystatin C-based eGFR from 110 to 101 ml/min/1.73 m², and combined creatinine-cystatin C eGFR from 111 to 103 ml/min/1.73 m² (all p < 0.005). Kidney dimensions increased stepwise with adiposity. KL exceeded the 97.5th percentile in 15-19% of participants depending on the reference standards, whereas KV was increased in 48-51% when age-/BSA-based, and 15% when height-based. Albuminuria was uncommon (<5% participants). KV showed significant associations with insulin (r = 0.27), uric acid (r = 0.33), systolic blood pressure (r = 0.33; all p < 0.001). In multivariable linear regression BMI-SDS was independently associated with KV (β = 0.29; 95% CI 0.22-0.36; p < 0.001), inclusion of kidney over-size significantly improved model fit.</p><p><strong>Conclusions: </strong>Excess adiposity is linked to marked kidney enlargement and BMI-related differences in filtration-marker-derived eGFR estimates. Increased KV is frequent despite low prevalence of albuminuria, supporting KV as a sensitive marker of early obesity-related kidney remodeling. The functional significance of lower estimated eGFR values requires confirmation using measured GFR methods.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related changes in adiposity and cardiometabolic disease risk: a longitudinal and prospective study in the UK Biobank.","authors":"Mathias Rask-Andersen, Valeria Lo Faro, Torgny Karlsson, Åsa Johansson","doi":"10.1038/s41366-026-02168-2","DOIUrl":"https://doi.org/10.1038/s41366-026-02168-2","url":null,"abstract":"<p><strong>Background/objectives: </strong>Body mass index (BMI) is widely used to assess obesity-related disease risk but does not capture important aspects of fat distribution and ectopic fat deposition. Here we assess age-related differences in magnetic resonance imaging (MRI)-derived body composition measures and their relevance for cardiometabolic disease risk.</p><p><strong>Subjects/methods: </strong>We analysed 36,831 UK Biobank participants (45-82 years), with MRI-derived measures, including 1,688 participants with longitudinal measures. Nine MRI-derived traits and five cardiometabolic outcomes were analysed: type 2 diabetes (T2DM), hypertension, hyperlipidaemia, myocardial infarction, and cerebral infarction. Cox regression was used to estimate the association between adiposity traits and clinical outcomes and stepwise Cox regression to determine the relative importance of the variables. Significant associations were validated using univariable and multivariable Mendelian randomization (MR).</p><p><strong>Results: </strong>At the initial imaging session, several MRI-derived traits, including visceral adipose tissue (VAT) volume and pancreatic and thigh muscle fat infiltration, were higher with age at assessment and increased within participants between imaging timepoints in the longitudinal sub-cohort, despite similar BMI. In contrast, liver and pancreas volume were lower in older participants. All MRI-derived traits were associated with at least one clinical outcome. However, after adjustment for multiple testing and for BMI, only T2DM and hyperlipidemia remained significant. Including MRI-derived traits alongside BMI improved risk prediction, particularly in males. VAT showed the strongest association and accounted for a substantial proportion of the T2DM risk traditionally attributed to BMI in both females and males, as supported by multivariable MR.</p><p><strong>Conclusions: </strong>Ageing is associated with progressive, depot-specific redistribution of body fat with increasing accumulation in metabolically harmful depots later in life. MRI-derived adiposity measures provide important insight into these risk-relevant patterns. Future clinical translation may depend on more scalable tools or biological markers that capture visceral and ectopic fat accumulation and improve cardiometabolic risk assessment beyond BMI.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life antibiotic use and children with overweight and obesity: a Dutch twin cohort study.","authors":"Rosa S Feil, Elise M A Slob, Jenny van Dongen, Simone Hashimoto, Bodine M A Gonggrijp, Ozair Abawi, Dorret I Boomsma, Anke H Maitland-van der Zee","doi":"10.1038/s41366-026-02164-6","DOIUrl":"https://doi.org/10.1038/s41366-026-02164-6","url":null,"abstract":"<p><p>The number of children with obesity has risen over the decades, becoming a major public health concern, also because of persistence into adulthood and morbidity. Early-life antibiotic use alters gut microbiota composition, potentially causing metabolic disturbances, increasing the number of children with obesity. To explore the association between early-life antibiotic use and the risk of developing overweight/obesity during childhood, we analyzed data from the Netherlands Twin Register, using a co-twin control design in outcome-discordant pairs to control for confounding due to shared environmental and/or genetic factors. This retrospective study included data from 34,142 twins aged 4.5-15.4 years. Any antibiotic use before age 2 was reported in 24.6% of children; 1.06% were children with obesity, and 9.23% were children with overweight/obesity based on sex- and age-specific BMI thresholds from the International Obesity Task Force and the World Health Organization. We evaluated outcomes for dichotomous and continuous data (BMI Z-scores), adjusting for sex, delivery mode, gestational age, birthweight, breastfeeding, maternal BMI, and parental education levels. No association was found between early-life antibiotic use and the risk of developing obesity (OR 0.82, 95% CI 0.60-1.14) or overweight/obesity (OR 1.00, 95% CI 0.90-1.12) during childhood. Matched co-twin analyses showed similar null results. Also, BMI Z-scores did not differ by antibiotic exposure. These findings suggest that early-life antibiotic use is not associated with an increased risk of overweight or obesity in childhood.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vutiglabridin overcomes the GLP-1 RA-associated weight-loss plateau to achieve normal body weight.","authors":"Hyeong Min Lee, Kamindu Gayashan Marakkalage, Sang Hyo Kim, Soonje Lee, Jae Ho Lee, Hyung Soon Park, Sang-Ku Yoo","doi":"10.1038/s41366-026-02161-9","DOIUrl":"https://doi.org/10.1038/s41366-026-02161-9","url":null,"abstract":"<p><strong>Background/objectives: </strong>Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective for body weight reduction, there remains a critical unmet need for complementary strategies that drive selective fat loss and sustain long-term weight reduction. This study aimed to investigate whether Vutiglabridin, a novel oral small-molecule anti-obesity drug, complements GLP-1 RAs to enhance therapeutic efficacy by selectively reducing fat mass and achieving normal body composition.</p><p><strong>Subjects/methods: </strong>6-week-old mice were fed a high-fat diet (60 kcal% fat) for 11 weeks to generate mice with diet-induced obesity (DIO) and then treated with GLP-1 RAs (Semaglutide, Liraglutide, or Exenatide) either alone or in combination with Vutiglabridin for 3-4 weeks.</p><p><strong>Interventions/methods: </strong>Body weight, food intake, fat mass, and lean mass were evaluated during treatment. For the drug discontinuation study, mice were administered Vutiglabridin, Semaglutide, or the combination for 4 weeks, after which treatment was withdrawn on Day 28 and body weight regain was monitored for 21 days.</p><p><strong>Results: </strong>In DIO mice treated with Semaglutide, weight loss attenuated, and body weight was maintained at a constant level after 2 weeks. In contrast, co-administration of Vutiglabridin overcame this attenuation of efficacy, enabling continuous weight reduction and achieving normal body composition. Vutiglabridin also resolved the diminishing weight-loss effect when combined with comparatively less potent appetite-suppressing GLP-1 RAs, including liraglutide and exenatide. In addition to normalizing body composition, Vutiglabridin mitigated the body weight and fat-mass regain that occurs following Semaglutide discontinuation.</p><p><strong>Conclusions: </strong>These findings demonstrate that Vutiglabridin can normalize body composition in combination with multiple GLP-1 RAs, highlighting its potential as a novel therapeutic option for obesity treatment.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}