International Journal of Obesity最新文献

{"title":"Cumulative abdominal obesity exposure and progressive risk of endometrial cancer in young women: a nationwide cohort study.","authors":"Min-Kyung Lee, Jung Heo, Jiyeon Ahn, Seo-Young Sohn, Jae-Hyuk Lee, Kyungdo Han, Whi-An Kwon, Yeon Jee Lee, Yong Sang Song","doi":"10.1038/s41366-025-01862-x","DOIUrl":"https://doi.org/10.1038/s41366-025-01862-x","url":null,"abstract":"<p><strong>Background: </strong>The incidence of endometrial cancer has been rising sharply among younger generations, paralleling the growing obesity epidemic in this age group. Abdominal obesity is currently being investigated as an indicator of adiposity and cancer risk, and its prevalence is increasing in young women. This study aimed to examine whether cumulative abdominal obesity exposure in young women was associated with the development of endometrial cancer.</p><p><strong>Methods: </strong>We used data from the South Korean National Health Insurance Service for women aged 20-39 years who had completed four consecutive annual health examinations between 2009 and 2012 and had no history of cancer at baseline. Participants were categorized into five groups based on the number of abdominal obesity exposures (waist circumference ≥ 85 cm). Exposure numbers ranged from 0 to 4, indicating the frequency of abdominal obesity across the four health examinations over 4 years. The primary outcome was newly diagnosed endometrial cancer, which was monitored until 2020, with a follow-up period of 7.12 years.</p><p><strong>Results: </strong>Among the 445,791 young women (mean [SD] age 30.82 [4.55] years), 302 (mean [SD], 32.79 [4.53] years) developed endometrial cancer. The cumulative incidence of endometrial cancer differed significantly according to the number of abdominal obesity exposures (log-rank test, P < .001). The incidence of endometrial cancer has progressively increased with abdominal obesity exposure. The multivariable-adjusted HRs for incident endometrial cancer were 1.480 (95% CI, 0.970-2.258), 2.361 (95% CI, 1.391-4.008), 4.114 (95% CI, 2.546-6.647), and 6.215 (95% CI, 4.250-9.088) for participants with exposure numbers of 1-4, respectively, compared with those with an exposure number of 0.</p><p><strong>Conclusion: </strong>In this population-based nationwide cohort study of young women, we observed a progressive increase in the risk of endometrial cancer with cumulative abdominal obesity exposure.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953930","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":"A Bayesian life-course linear structural equations model (BLSEM) to explore the development of body mass index (BMI) from the prenatal stage until middle age.","authors":"Evangelia Tzala, Marco Banterle, Ville Karhunen, Tom A Bond, Mimmi Tolvanen, Marika Kaakinen, Sylvain Sebert, Alex Lewin, Marjo-Riitta Jarvelin","doi":"10.1038/s41366-025-01857-8","DOIUrl":"https://doi.org/10.1038/s41366-025-01857-8","url":null,"abstract":"<p><strong>Objective and methods: </strong>We have developed a novel Bayesian Linear Structural Equations Model (BLSEM) with variable selection priors (available as an R package) to build directed acyclic graphs to delineate complex variable associations and pathways to BMI development. Conditional on standard assumptions used in causal inference, the model provides interpretable estimates with uncertainty for natural direct, indirect (mediated) and total effects.</p><p><strong>Results: </strong>We showcase our method using data on 4119 offspring followed from the pre-pregnancy period to age 46 years (y) in a Finnish population-based birth cohort. The BLSEM enabled efficiently to analyse all available data over the long-time span, identifying factors to distil potential causal pathways contributing to adult BMI development. All of the associations between early childhood and adolescence variables with adult BMI at 46 y (BMI46) were indirect via multiple paths. For example, maternal prepregnancy BMI, smoking and socioeconomic position are associated with BMI46 through 35, 31 and 26 paths. Another notable feature was that the contribution of very early life factors, particularly prenatal, was captured by growth patterns along childhood, which were the strongest early predictors of middle age BMI46 (the age at adiposity rebound (AgeAR), early growth parameters between the AgeAR to 11 y). BMI and blood pressure measured 15 y earlier also predicted BMI46, all other factors held constant. Genetic predisposition by the polygenic risk score for BMI showed an indirect effect that became apparent at AgeAR and thereafter.</p><p><strong>Conclusions: </strong>The Bayesian approach we present and the BLSEM software developed advances methodologies for the analysis of complex, multifaceted life-course data prior to the estimation of potential causal pathways. Our results, although exploratory in nature, suggest that the effective interventions to tackle adverse BMI development could be designed throughout childhood, though the period by AgeAR may be paramount. We feature the importance of integrated life-course analyses that help to understand the contribution of life-stage factors of development.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953969","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":"The long-term effect of metabolic bariatric surgery on innate immune cell phenotype and function.","authors":"Julia van Tuijl, Debby Vreeken, Wieteke Broeders, Benjamin Cossins, Liesbeth van Emst, Florine Seidel, Rinke Stienstra, Yang Li, Leo A B Joosten, Mihai G Netea, Eric J Hazebroek, Robert Kleemann, Amanda J Kiliaan, Siroon Bekkering, Niels P Riksen","doi":"10.1038/s41366-025-01886-3","DOIUrl":"https://doi.org/10.1038/s41366-025-01886-3","url":null,"abstract":"<p><strong>Objectives: </strong>Obesity is an important risk factor for atherosclerotic cardiovascular disease. This cardiovascular risk remains increased even after substantial weight loss by bariatric surgery. Innate immune cells are important regulators of atherogenesis and can adopt a long-term hyperinflammatory phenotype via epigenetic reprogramming, called \"trained immunity\". In this translational observational case-cohort study, we investigated the persistence of innate immune cell hyperresponsiveness following bariatric surgery, and explored the potential contribution of adipose tissue in ex vivo models.</p><p><strong>Subjects/methods: </strong>In a cohort of 27 patients with obesity blood was drawn before and six months after bariatric surgery, and compared to 20 healthy subjects with normal body weight. We assessed monocytes using flow cytometry, functional assays, and RNA sequencing and chromatin immunoprecipitation. In an accompanying series of in vitro studies, healthy donor monocytes were exposed for 24 h to adipose tissue obtained from patients with obesity during bariatric surgery. Cytokine production capacity was assessed after one week.</p><p><strong>Results: </strong>In our case-cohort study, although leukocyte numbers and systemic inflammatory markers such as hs-CRP decreased after bariatric surgery to the level of normal weight control subjects, the hyperresponsive pro-inflammatory monocyte phenotype was only partially reverted six months after bariatric surgery, which aligned with the RNA expression profiles. Exposure of monocytes to adipose tissue obtained from patients with obesity induces a persistent augmented cytokine production capacity.</p><p><strong>Conclusions: </strong>Although in patients with obesity, six months after bariatric surgery systemic inflammatory markers and leukocyte numbers are decreased to the levels observed in healthy lean subjects, there is still a residual functional and transcriptional hyper-inflammatory monocyte phenotype. This might be caused, at least in part, by the capacity of adipose tissue to induce long-term pro-inflammatory effects in monocytes. These finding help to understand the long-term effects of obesity and bariatric surgery on cardiovascular health.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953970","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":"Association between overweight and obesity determined by body mass index and overall survival in patients with metastatic prostate cancer: a meta-analysis.","authors":"Feilun Cui, Yueshi Zhang, Ziyan Liu, Changfeng Man, Dandan Gong, Yongjing Zhou, Yu Fan","doi":"10.1038/s41366-025-01883-6","DOIUrl":"https://doi.org/10.1038/s41366-025-01883-6","url":null,"abstract":"<p><strong>Background: </strong>Studies on the association between obesity and mortality in patients with prostate cancer have yielded inconclusive findings. This meta-analysis aimed to evaluate the association between overweight/obesity determined by body mass index (BMI) and overall survival (OS) in patients with metastatic prostate cancer (mPC).</p><p><strong>Methods: </strong>A systematic search was conducted in the PubMed, Web of Science, and Embase databases until February 2025. Studies that evaluated the association between overweight/obesity and OS in patients with mPC were considered.</p><p><strong>Results: </strong>Fifteen studies reported in 13 articles, including 18,280 patients, were identified. The overall pooled adjusted HR for OS was 0.79 (95% CI 0.73-0.85) for patients with overweight/obesity versus those with normal weight. The pooled adjusted HR for OS was 0.81(95%CI 0.75-0.87) for overweight and 0.78 (95%CI 0.67-0.90) for obesity. Furthermore, the association of overweight (HR 0.78; 95% CI 0.71-0.85) and obesity (HR 0.73; 95% CI 0.59-0.90) with OS was more pronounced in patients with metastatic castration-resistant prostate cancer (mCRPC). Additionally, each 1-unit increase in BMI was associated with a 4% (95% CI 1.0-8.0%) improvement in OS.</p><p><strong>Conclusion: </strong>Patients with mPC who have overweight or obesity, as defined by BMI, are associated with improved overall survival, particularly in those with mCRPC.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859106","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":"Weight change from incretin-based weight loss medications across categories of second-generation antipsychotics.","authors":"Jithin Sam Varghese, David R Goldsmith, Robert O Cotes, Vishnu Ravikumar, Mohammed K Ali, Francisco J Pasquel","doi":"10.1038/s41366-025-01885-4","DOIUrl":"https://doi.org/10.1038/s41366-025-01885-4","url":null,"abstract":"<p><strong>Objective: </strong>Patients prescribed second-generation antipsychotics (SGA) are at risk of antipsychotic induced weight gain (AIWG). The objective was to estimate weight changes after prescription of incretin-based weight loss medications by category of expected AIWG: high (olanzapine, clozapine), intermediate (risperidone, quetiapine, paliperidone) and low (e.g., asenapine, aripiprazole).</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using electronic health records (June 2021-December 2023) from Epic Cosmos for adults (≥18 years) without diabetes, prescribed SGA, and eligible for incretin-based weight loss medications. We studied changes in weight (kg) and the probability of at least 5% weight loss after 6 months of prescription of incretin-based medications by categories of AIWG.</p><p><strong>Results: </strong>The analytic sample (n = 66,574) were aged 51.9 years (SD: 17.7), with average BMI of 39.5 kg/m² (SD: 7.7). Those prescribed incretin-based medications lost -2.17 kg (95% CI: -2.49, -1.84), and were 1.71 (95% CI: 1.63, 1.80) times more likely to achieve 5% weight loss, relative to those who didn't receive prescriptions. Weight loss was greater among those prescribed SGAs of low AIWG (-3.02 kg, 95% CI: -3.29, -2.74), relative to those prescribed high AIWG (-1.33 kg, 95% CI: -2.04, -0.62).</p><p><strong>Conclusions: </strong>Semaglutide and tirzepatide induce weight loss among those prescribed SGAs, with lower effectiveness in those prescribed higher AIWG SGAs.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859107","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":"Effectiveness of a telephone-based randomised clinical trial targeting obesity risk of preschool-aged children: An extension study during the COVID-19 pandemic.","authors":"Li Ming Wen, Huilan Xu, Zoe Chen, Alison Hayes, Philayrath Phongsavan, Sarah Taki, Erin Kerr, Danielle Jawad, Lisa Simone, Chris Rissel, Louise A Baur","doi":"10.1038/s41366-025-01869-4","DOIUrl":"https://doi.org/10.1038/s41366-025-01869-4","url":null,"abstract":"<p><strong>Background: </strong>There is a great need for determining the effectiveness of telephone-based early obesity interventions targeting preschool-aged children. This was particularly important during the COVID-19 pandemic when most face-to-face health promotion programs were suspended. The aim of this study was to determine the effects of a two-year telephone-based intervention on body mass index (BMI), eating habits, active play, and screen time behaviours among preschool-aged children.</p><p><strong>Methods: </strong>We conducted an extension study to a randomised controlled trial (RCT) with 662 mother-child dyads at ages 2-3 years in 2019-20 in the Greater Sydney metropolitan area of New South Wales (NSW), Australia. In 2020-22, we extended the RCT for another two years, with one-year intervention (3-4 years) and one-year follow-up (4-5 years). Participants remained in the same group allocation as the original trial. The intervention comprised five nurse-led telephone support calls and SMS plus mailed intervention booklets to mothers to promote the health behaviours of their children from ages 2 to 4 years. The primary outcome was children's BMI, with weight and height measured at ages 3, 4, and 5 years. We conducted intention-to-treat analysis with a multiple imputation approach. Mixed linear models were built to compare the outcomes between intervention and control groups. Sub-group analysis by household income was also conducted.</p><p><strong>Results: </strong>Of the 662 mothers, 537 (81%), 491 (74%), and 405 (61%) completed the assessments when their children were 3, 4, and 5 years old. The intervention was significantly associated with a lower mean BMI: 15.90 (SE 0.08) vs. 16.20 (SE 0.08), difference -0.30 (95% CI: -0.59 to -0.01, P = 0.039). This association was stronger among low-income families, difference -0.57 (95% CI: -1.05 to -0.10, P = 0.018).</p><p><strong>Conclusions: </strong>The two-year telephone-based intervention was associated with decreased mean BMI of preschool-aged children. Telephone-based support for mothers could reduce obesity risk in preschool-aged children, particularly among low-income families.</p><p><strong>Trial registration: </strong>The original RCT is registered with the Australian Clinical Trial Registry (ACTRN12618001571268).</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855168","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":"Does a heritable common latent factor explain body mass index, percent body fat, and waist circumference across childhood?","authors":"Eva M Bartsch, Sierra Clifford, Mary C Davis, Leah D Doane, Kathryn Lemery-Chalfant","doi":"10.1038/s41366-025-01864-9","DOIUrl":"10.1038/s41366-025-01864-9","url":null,"abstract":"<p><strong>Background/objectives: </strong>Empirical data consistently suggest high heritability estimates for adiposity, with heritability peaking during childhood. However, no study has considered the potentially shared genetic and environmental etiologies of the three most commonly used adiposity metrics - body mass index (BMI), waist circumference, and percent body fat. We examined the genetic and environmental contributions to BMI, percent body fat, and waist circumference, and the extent to which their genetic and environmental variances overlap during middle childhood.</p><p><strong>Subjects/methods: </strong>We examined the genetic and environmental contributions to BMI, percent body fat, and waist circumference in a community sample of twin children (N = 254-326 pairs; female=47.8-49.9%; Non-Hispanic White=51.9-59.5%, Hispanic=29.5-35.7%) studied at ages 8, 9, 10, and 11 years by comparing the fit of two models: the independent and common pathway models.</p><p><strong>Results: </strong>The common pathway model yielded the most parsimonious fit, indicating that covariance between indicators was best represented by a single highly heritable common latent factor. This common factor explained 97-98% of the variance in BMI regardless of age, whereas indicator-specific genetic and environmental influences explained 10-17% of the variance in percent body fat and 14-29% of the variance in waist circumference.</p><p><strong>Conclusions: </strong>Our findings support a highly heritable common adiposity factor for BMI, body fat, and waist circumference in a community sample of youth, and suggest that BMI is a useful measure of adiposity in large-scale epidemiological studies with limited resources in middle childhood. When resources permit, including other adiposity indicators such as percent body fat and waist circumference can provide more precise assessments for specific subgroups. Our study highlights the need for individualized approaches to managing childhood adiposity, recognizing the strong genetic component and the variability in how children respond to their environments. Theories of the etiology of childhood obesity should accommodate genetic influences to optimize prevention and intervention efforts.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855167","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":"\"Just put in a little more effort\": the help-seeking experience of patients living with obesity.","authors":"Lucas Schreurs, Carla De Smedt, Ellen Goris, David Unuane, Martijn Schoneveld, Nele Steenackers, Sofia Pazmiño, Inge Gies, Bart Van der Schueren, Diederik De Cock","doi":"10.1038/s41366-025-01867-6","DOIUrl":"https://doi.org/10.1038/s41366-025-01867-6","url":null,"abstract":"<p><strong>Background: </strong>Early detection of the disease obesity and support for patients living with obesity could improve the success of obesity treatment and management. The factors influencing the delay in obesity treatment, defined as the period between obesity onset and treatment start, are largely unknown. The aim of our study is to explore the help-seeking behavior of PwO towards obesity treatment.</p><p><strong>Methods: </strong>In this cross-sectional qualitative study, consecutive patients visiting the obesity clinic of the University Hospitals of Brussels between December 2023 and April 2024 were invited to participate. PwO were interviewed, and data were transcribed and analysed using thematic analysis.</p><p><strong>Results: </strong>A total of 18 PwO (61% female, median age 37 years, (IQR: 23.5-57.5)) were interviewed. The journey of PwO towards obesity care seemed complex with multiple HCPs involved. Four themes were identified as triggers for seeking obesity care: Referral from primary care, family, friends and schools; Health complications; Financial burden of living with obesity; and Increased internal motivation. Three themes were identified as factors increasing treatment delay: Inefficient referral; Pressure from society to try lifestyle approaches first; and Challenges to overcome barriers for metabolic surgery. Inefficient referral from dietitians to multidisciplinary obesity treatment was identified as the main cause of treatment delay. PwO feel discouraged by the limited effectiveness of dietary guidance, leading to disengagement from the healthcare system.</p><p><strong>Conclusion: </strong>Our findings identify several key barriers contributing to treatment delays for patients with obesity. People living with obesity emphasized the need for an obesity care pathway and improved communication among primary care providers, allied health professionals, and collaborating centres for obesity management (COMs) to reduce the time required to access appropriate obesity treatment. Additionally, societal perceptions framing obesity as a result of a lack of willpower were reported by patients with obesity as a barrier to seeking care.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855166","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":"Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis.","authors":"Abdulrahman Ismaiel, Giuseppe Guido Maria Scarlata, Irina Boitos, Daniel-Corneliu Leucuta, Stefan-Lucian Popa, Nahlah Al Srouji, Ludovico Abenavoli, Dan L Dumitrascu","doi":"10.1038/s41366-025-01859-6","DOIUrl":"https://doi.org/10.1038/s41366-025-01859-6","url":null,"abstract":"<p><strong>Introduction: </strong>Overweight and obesity are major global health issues, increasing disease risk and straining healthcare systems. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for weight loss but cause gastrointestinal side effects, affecting adherence. Research often focuses on diabetics, leaving a gap in understanding their effects on non-diabetic individuals with overweight or obesity. This systematic review and dose-response network meta-analysis addresses this gap, analyzing gastrointestinal adverse events from GLP-1 RAs in non-diabetic subjects with overweight or obesity.</p><p><strong>Methods: </strong>We evaluated available evidence by searching PubMed and EMBASE databases, according to specific inclusion and exclusion eligibility criteria to evaluate gastrointestinal adverse events associated with GLP-1 RAs in non-diabetic individuals with overweight or obesity. Quality assessment of included studies was conducted using Cochrane Collaboration's tool.</p><p><strong>Results: </strong>Thirty-nine articles were included in the review showing a total number of 33,354 individuals. Nausea, vomiting, diarrhea, and constipation were the most common gastrointestinal adverse effects. All evaluated GLP-1 RAs led to a significant increase in nausea risk, with orforglipron showing the highest risk, followed by exenatide, tirzepatide, semaglutide, and liraglutide. Additionally, liraglutide, orforglipron, semaglutide, and tirzepatide were associated with increased vomiting risk, while cagrilinitide and exenatide showed no significant increase. Exenatide, cagrilinitide, orforglipron were not associated with diarrhea risk. Finally, semaglutide and liraglutide were associated to increased constipation risk, while cagrilinitide and exenatide showed no significant increase.</p><p><strong>Conclusions: </strong>GLP-1 RAs showed several adverse gastrointestinal effects in non-diabetic patients with overweight or obesity. Understanding the different risk profiles of GLP-1 RAs helps clinicians make informed treatment decisions by balancing therapeutic benefits with potential side effects.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144846561","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":"Interleukin-33 promotes lipolysis of adipocytes and protects male mice against obesity via activation of β-adrenergic receptor signaling.","authors":"Qianjiang Chen, Ke Ding, Mengfan Li, Rui Ma, Jian Lin, Jialin Guan, Jingli Lu","doi":"10.1038/s41366-025-01873-8","DOIUrl":"https://doi.org/10.1038/s41366-025-01873-8","url":null,"abstract":"<p><strong>Background: </strong>Targeting intracellular lipolysis represents a therapeutic potential for treating metabolic disorders such as obesity. Interleukin (IL)-33 has been shown to exert anti-obesity effects by reducing inflammation and restricting adipocyte hypertrophy.</p><p><strong>Methods: </strong>In this study, male mice on a high-fat diet (HFD) were treated with IL-33 once every 2 days for 2 weeks. 3T3-L1 cells were treated with IL-33 to verify the down-stream effect of β1-AR activation on the adipose cells.</p><p><strong>Results: </strong>IL-33 treatment led to a reduction in adipose tissue mass and a decreased in lipid deposition in male mice with obesity, accompanied by activation of β-adrenergic receptor (β-AR) signals. Immunostaining for tyrosine hydroxylase (TH) revealed an increase of TH within the adipose tissue in male mice. Metabolomic analysis showed that IL-33 induced a distinct metabolic profile in differentiated adipocytes, with significant changes in metabolites related to lipolysis pathways. Supplementation with β1-AR inhibitor significantly inhibited IL-33-induced p-HSL and p-PKA activation. Compared to IL-33 alone, β1-AR inhibitor reduced glycerol release and increased accumulation of lipid droplets. We also illustrated the fatty acids (FAs) process by tracking FA trafficking, and found that the labeled FA localized lipid droplets (LDs) in mature adipocytes but shifted from LDs to mitochondria at 20 ng/mL IL-33.</p><p><strong>Conclusion: </strong>We summarized that IL-33 regulated mature adipocyte metabolism and enhanced lipolysis in male mice via activation of the β-AR/cAMP/PKA/HSL signaling pathway. However, given that sex is a significant determinant in obesity, future studies should investigate potential sex-specific effects of IL-33 in metabolic regulation.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835026","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}