International Journal of Obesity最新文献

{"title":"Adherence to the Eatwell Guide and associations with markers of adiposity: a prospective analysis within the UK Biobank cohort.","authors":"Alex Griffiths, Sarah Gregory, Fiona C Malcomson, Marie Spreckley, Jamie Matu, Louisa Ells, Oliver M Shannon","doi":"10.1038/s41366-026-02190-4","DOIUrl":"https://doi.org/10.1038/s41366-026-02190-4","url":null,"abstract":"<p><strong>Background: </strong>Obesity remains a major public health concern in the UK, contributing towards increased disease risk and premature mortality. The Eatwell Guide - the UK's health eating model - is widely applied in policy and practice, yet evidence linking adherence to this dietary pattern with adiposity is limited. Similarly, understanding whether associations differ across population subgroups, including by level of genetic risk for obesity, is essential to inform equitable and effective dietary guidance.</p><p><strong>Methods: </strong>In 156,764 participants from the UK Biobank, we explored cross-sectional and prospective associations between adherence to the Eatwell Guide and markers of adiposity (BMI, waist circumference, a body shape index [ABSI], and total and trunk body fat percentage). Differences between population sub-groups including by genetic risk, age, sex, physical activity level and socioeconomic status were explored.</p><p><strong>Results: </strong>Higher Eatwell Guide adherence was cross-sectionally associated with lower BMI (β = -0.032, SE = 0.001, p < 0.001), with higher adherence associated with 25% lower odds of overweight/obesity versus lower adherence (OR = 0.75, 95% CI 0.73-0.77, p < 0.001). Prospectively, greater Eatwell Guide adherence predicted more favourable BMI trajectories over time (β = -0.008, SE = 0.001, p < 0.001). Similar, significant associations were observed for waist circumference, ABSI, and total and trunk body fat percentage (all p < 0.05) and were broadly consistent across key population sub-groups.</p><p><strong>Conclusions: </strong>Higher Eatwell Guide adherence was associated with beneficial changes in multiple markers of adiposity over time. These associations were consistent across key demographic groups, highlighting the potential role of adhering to UK healthy eating recommendations as part of weight management strategies in the UK.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766567","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":"High resolution lipoprotein subfraction profiling identifies obesity associated distributional changes in LDL and HDL subfractions and particle ratios.","authors":"Novia Minaee, Reika Masuda, Philipp Nitschke, Drew Hall, Jennie Hui, Michael L Hunter, Leon Flicker, Graeme J Hankey, Osvaldo P Almeida, Dick C Chan, Gerald F Watts, Muhammad Saeed Ahmad, Huda M Alkreathy, Zoheir Abdullah Dhamanouri, Hartmut Schäfer, Manfred Spraul, Claire Cannet, John P Beilby, Bu B Yeap, Oscar Millet, Julien Wist, Jeremy K Nicholson, Samantha Lodge, Elaine Holmes","doi":"10.1038/s41366-026-02172-6","DOIUrl":"https://doi.org/10.1038/s41366-026-02172-6","url":null,"abstract":"<p><strong>Background: </strong>Obesity is associated with adverse alterations in lipoprotein profiles and increased cardiometabolic risk, yet standard clinical lipid measures provide limited resolution of the underlying lipoprotein structure. Here, we perform a population-level characterisation of the impact of obesity on the high-resolution blood lipoprotein subfraction profile.</p><p><strong>Methods: </strong>Lipoprotein profiles were investigated in an Australian cohort (n = 1806) stratified by Body Mass Index (BMI) (healthy weight, overweight, obese). The composition and particle number of lipoproteins and their subfractions were quantified (n = 112 parameters) using ¹H NMR spectroscopy. Associations between BMI, lipoprotein subfractions, and particle number ratios were evaluated. Key BMI-associated ratios were validated in a second Australian cohort (n = 1313) RESULTS: Participants with obesity had significantly higher particle concentrations of VLDL and IDL and lower HDLs, while total LDL concentration was similar between the BMI categories. Notably, obesity was associated with a marked redistribution of LDL subfractions, with a shift from larger, buoyant LDL1-3 particles to smaller, dense LDL4-6 particles, accompanied by a similar shift in HDL subfractions, with proportionally lower concentrations of HDL1-3 particles in the high BMI group. An inverse association between BMI was found for two LDL particle number ratios (LDL1-3:LDL4-6 and LDL2:LDL5) and one HDL ratio (HDL1:HDL4), which demonstrated good discriminatory power for obesity status (AUROCs 0.70-0.74).</p><p><strong>Conclusions: </strong>The pattern of lipoprotein subfraction redistribution in participants with obesity was consistent across cohorts. These subfractional changes offer enhanced resolution compared with conventional lipid and lipoprotein measures and may contribute to improved cardiovascular risk stratification in individuals with obesity.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764979","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":"Obesity-associated unfolded protein response, oxidative stress, and NRF2 signaling.","authors":"Şeyma Özgür, Alessandro Medoro, Sergio Davinelli, Nicole Bender, Luciano Saso, Pelin Telkoparan-Akillilar","doi":"10.1038/s41366-026-02188-y","DOIUrl":"10.1038/s41366-026-02188-y","url":null,"abstract":"<p><p>Obesity has become a major global health problem. It is characterized by increased body fat storage and is associated with excessive food intake. Although obesity is often thought of as a simple problem involving fat accumulation in the body, it is a complex disease that alters cellular defense systems and causes low-grade chronic inflammation, which can contribute metabolic syndrome. Even though obesity is an inflammatory disease, an increase in the formation of reactive oxygen species (ROS) is also observed due to excess nutrition. Excessive ROS production contributes to obesity progression and endoplasmic reticulum (ER) stress. In response to oxidative stress, cells activate antioxidant defense mechanisms either through unfolded protein response (UPR) pathways or via UPR-independent signaling pathways. Nuclear factor-erythroid 2-related factor-2 (NRF2) controls the transcription of multiple genes encoding antioxidant and cytoprotective proteins. NRF2 is of interest in obesity research as it can be activated with or without UPR elements and plays a role in the regulation of antioxidant response. Targeting NRF2 through multiple approaches has been shown to reduce or prevent obesity and obesity associated metabolic complications. This review examines the molecular mechanisms of NRF2 activation in obesity, with particular focus on its bidirectional crosstalk with the UPR and discusses the therapeutic implications of targeting this axis in obesity and its related metabolic dysfunction.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727770","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":"Cathepsin D-driven IL2RG-JAK2 signal hijacking disrupts hepatic insulin action: mechanism-grounded proof that targeting cathepsin D prevents prediabetes.","authors":"Lingling Ding, Peng Jiang, Yuxi Zou, Yanyan Chen, Ting Chen, Shujin Wang, Changlong He, Hui Qian","doi":"10.1038/s41366-026-02193-1","DOIUrl":"10.1038/s41366-026-02193-1","url":null,"abstract":"<p><strong>Background: </strong>Hepatic insulin resistance (HIR), an early feature of prediabetic, plays a pivotal role in disrupting glucose homeostasis. Clarifying the mechanisms underlying HIR is critical for diabetes prevention. Our previous study has discovered the positive correlations between plasma cathepsin D (CTSD) activity and the degree of HIR in people with obesity. Accordingly, this study investigates the roles of CTSD in the underlying mechanisms involving HIR and impaired glucose homeostasis.</p><p><strong>Methods: </strong>The samples from people/mice with obesity/MASLD (metabolic dysfunction- associated steatotic liver disease) and HIR cellular models were used for assessing mRNA expression/protein expressions/activity of CTSD. RNA sequencing data from hepatocytes were then performed to disclose the potential mechanism of CTSD-induced HIR. Next, the plasmids of CTSD overexpression and CTSD knockdown were constructed to verify the effects and mechanisms of CTSD in HIR. Lastly, the CTSD inhibitor Pepstatin A (PepA) was administrated to mice with obesity/MASLD to explore the preventive effect of targeting CTSD on prediabetes.</p><p><strong>Results: </strong>Significant increases in mRNA expression, protein levels, and activity of CTSD were observed in individuals and mice with obesity/MASLD, as well as in HIR cell models, compared with controls. Furthermore, we found that increased CTSD or overexpressing CTSD could trigger HIR mediated by the IL2RG-JAK2 axis, thus disturbing hepatic insulin signaling transduction. Inhibiting CTSD with PepA or knocking down CTSD markedly improved HIR and rebalanced glucose metabolism in mice with obesity/MASLD and HIR cell models.</p><p><strong>Conclusion: </strong>Altogether, these current findings implicate that increased CTSD suppresses hepatic insulin sensitivity via activating the IL2RG-JAK2-STAT3 axis, highlighting CTSD inhibition as an attractive preventative strategy for prediabetes. CTSD-centered IL2RG-JAK2 axis interruption as a precision strategy to rescue hepatic insulin signaling and halt prediabetes progression.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721619","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":"Food noise as a missing piece in obesity treatment: toward an integrated intervention framework.","authors":"Abu Ansar Md Rizwan, Shannon Galyean","doi":"10.1038/s41366-026-02185-1","DOIUrl":"10.1038/s41366-026-02185-1","url":null,"abstract":"","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724802","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":"Adolescent weight gain trajectories and their associations with biological aging: a genetically informed study.","authors":"Anni Pitkänen, Anna Kankaanpää, Emma Raitoharju, Saara Marttila, Leo-Pekka Lyytikäinen, Pashupati P Mishra, Nina Mononen, Tuija Tammelin, Juha Mykkänen, Katja Pahkala, Suvi Rovio, Laura Joensuu, Miina Ollikainen, Jorma Viikari, Olli Raitakari, Terho Lehtimäki, Elina Sillanpää","doi":"10.1038/s41366-026-02194-0","DOIUrl":"10.1038/s41366-026-02194-0","url":null,"abstract":"<p><strong>Background: </strong>High body mass index (BMI) in adolescence is associated with accelerated biological aging, which might predict the onset of obesity-related diseases before they develop. Genetic factors may shape both adolescent BMI and weight trajectories.</p><p><strong>Methods: </strong>Participants were from the Young Finns Study (n = 3 596, ages 3-18 at baseline), followed from 1980 to 2018-2020. Biological aging was estimated using DNA methylation based epigenetic clocks DunedinPACE (years/calendar year) and PC-GrimAge (years) at three follow-ups (ages 15-56, n = 2045). Genetic predispositions to BMI and childhood body size were quantified using polygenic risk scores (PRSs) (941 and 286 genetic variants). BMI trajectories were modelled from BMI measured at ages 9, 12, 15 and 18 using latent growth curve modelling. Path analysis was used to examine whether genetic liability to BMI is associated with biological aging and if BMI trajectories in adolescence mediate this association. The causal effect of genetically predicted adolescent BMI on biological aging in adulthood was examined with Mendelian randomisation (MR) using individual-level data.</p><p><strong>Results: </strong>Higher level of adolescent BMI partly mediated the association between higher BMI-PRS and accelerated biological aging from late adolescence to middle adulthood. MR analyses supported a positive causal effect from genetically predicted adolescent BMI on biological aging, and the causal effect was more consistent when DunedinPACE was used to measure biological aging in 2011 (causal estimate = 0.020 [95% CI = 0.008, 0.031]) and 2018 (0.019 [0.003, 0.035]).</p><p><strong>Conclusions: </strong>Our findings indicate that high BMI in adolescence may accelerate biological aging, especially in individuals with a genetic predisposition to high BMI. Adolescents with a genetic susceptibility to high BMI and elevated BMI might be prone to obesity-related health risks, highlighting early prevention strategies' importance.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726162","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":"High body mass index within the normal weight range and risk of type 2 diabetes and hypertension in US and Europe: a systematic review and meta-analysis.","authors":"Ahmad Jayedi, Dagfinn Aune, Sakineh Shab-Bidar","doi":"10.1038/s41366-026-02183-3","DOIUrl":"10.1038/s41366-026-02183-3","url":null,"abstract":"<p><strong>Background/objective: </strong>Clinical guidelines suggest body mass index (BMI) thresholds of ≥25 kg/m² to identify individuals at elevated risk of type 2 diabetes and (T2D) hypertension, however, growing evidence suggests that higher BMI values within the normal weight range may also be associated with increased risks.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed and Scopus, with an updated PubMed search through October 2025, to identify cohort studies from the US and Europe that reported risk estimates of T2D or hypertension for higher normal weight BMI values (e.g., 22.5-24.9 kg/m²) compared with lower normal weight BMI values. Asian studies were excluded because of lower BMI thresholds in Asian populations. Random-effects meta-analysis was performed to estimate summary relative risks (RRs) and 95%CIs.</p><p><strong>Results: </strong>Eleven cohort studies were included, with 23% of participants and 17% of cases being classified as having high normal weight BMI values (22.5-24.9 kg/m²). Compared with lower BMI values within the normal weight range, high normal weight BMI values were associated with a greater risk of T2D (RR = 1.78, 95% CI: 1.30-2.45, I² = 98%; n = 10 studies with 1,818,036 participants and 84,414 cases; moderate certainty evidence). Evidence for hypertension was limited, based on three US cohort studies (RR = 1.42, 95% CI: 1.33-1.51, I² = 0; n = 3 studies with 129,046 participants and 22,254 cases; low certainty evidence).</p><p><strong>Conclusions: </strong>Compared with lower normal weight BMI values, higher BMI within the normal range was associated with a higher risk of T2D and hypertension, suggesting that current BMI classifications may not fully capture the increased risk among individuals at the upper end of the normal weight spectrum. If replicated, the findings may justify reconsideration of BMI thresholds to better reflect the higher cardiometabolic risk observed among individuals with high normal weight BMI.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722293","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":"Epigenetic age acceleration and metabolic syndrome among Hispanic/Latino adults: Hispanic Community Health Study/Study of Latinos (HCHS/SOL).","authors":"Sheroi Johnson, Jorge Gonzalez-Mejia, Jasmine K Aqua, Sydney Pritchard, Robert Kaplan, Jianwen Cai, Carmen R Isasi, Krista M Perreira, Christina Cordero, Linda C Gallo, Humberto Parada, Karen N Conneely, Shakira F Suglia","doi":"10.1038/s41366-026-02187-z","DOIUrl":"10.1038/s41366-026-02187-z","url":null,"abstract":"<p><strong>Introduction: </strong>We tested the bidirectional association between epigenetic age acceleration (EAA), a marker of biological aging, and metabolic syndrome (MetS), a cluster of conditions that together increase the risk of type 2 diabetes, cardiovascular disease, and other chronic conditions, at different time points.</p><p><strong>Methods: </strong>A random sample of 962 Hispanic/Latino adults participating in the Hispanic Community Health Study/Study of Latinos were included in the analyses. At baseline, the mean age was 44.8 years, 61.5% of participants were female, and prevalence of MetS was 35.4%. DNA methylation was measured from whole blood, at two different time points six years apart, using the Illumina EPIC BeadChip and epigenetic age and EAA were calculated using the PhenoAge, GrimAge, and DunedinPACE algorithms. MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III guidelines, in which a diagnosis is met when participants meet at least 3 of the 5 conditions: elevated waistline/abdominal obesity, high blood pressure, high blood sugar levels, high blood triglycerides, and low high-density lipoprotein (HDL) cholesterol.</p><p><strong>Results: </strong>In cross-sectional analyses, higher PhenoAA (PR, 95% CI: 1.03, 1.01, 1.05), GrimAA (PR, 95% CI: 1.05, 1.01, 1.09), and DunedinPACE values (PR, 95% CI: 1.03, 1.02, 1.04) were associated with higher MetS prevalence. Over an average follow-up of six years, higher DunedinPACE values at baseline were associated with higher risk of incident MetS (Risk Ratio (RR), 95% CI: 1.04, 1.02, 1.05). Faster DunedinPACE rates (vs. average) were associated with higher risk of incident MetS (RR, 95% CI: 1.44, 1.07, 1.94), whereas slower DunedinPACE rates (vs. average) were associated with lower risk (RR, 95% CI: 0.44, 0.23, 0.87).</p><p><strong>Conclusion: </strong>The study suggests EAA is a potential indicator of both prevalent and incident MetS among Hispanic/Latino adults.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of critical brain regions for young adults with obesity and their relationships with impulsivity using machine learning based on neuroanatomical features.","authors":"Guanjinghui Xu, Junhao He, Junjie Zhao, Yang Wang, Hui Xu","doi":"10.1038/s41366-026-02184-2","DOIUrl":"https://doi.org/10.1038/s41366-026-02184-2","url":null,"abstract":"<p><strong>Background: </strong>Prior obesity neuroimaging studies used univariate methods and small samples, limiting reproducibility. Employing a large-scale dataset and a two-stage machine learning framework, we identified neuroanatomical signatures of obesity and evaluated their population-level associations with delay discounting impulsivity.</p><p><strong>Methods: </strong>We enrolled 243 young adults with obesity and 475 healthy-weight controls from the Human Connectome Project S1200 dataset. Cortical surface area, cortical thickness, and subcortical gray matter volume were extracted using surface-based morphometry. Support vector machine (SVM) classifiers discriminated obesity from healthy weight based on neuroanatomical features, with interpretability assessed via SHapley Additive exPlanations (SHAP). Partial correlations evaluated associations between the 15 SVM-selected features and the area under the curve (AUC) of delay discounting (DD) in the full sample. Normative modeling examined if the obesity group deviated from brain-structure-based expectations of AUC-DD.</p><p><strong>Results: </strong>The neuroanatomical-only SVM achieved a receiver operating characteristic (ROC-AUC) of 0.648; adding demographic and cognitive covariates improved it to 0.740. SHAP highlighted the superior parietal, entorhinal, medial orbitofrontal, posterior cingulate, and rostral anterior cingulate cortices. Ten of the top 15 features were significantly associated with AUC-DD, and all in the expected direction. The obesity group showed systematically higher DD impulsivity than predicted impulsivity by brain structures alone.</p><p><strong>Conclusions: </strong>Distributed neuroanatomical features in prefrontal, medial temporal, cingulate, and parietal cortices discriminated obesity and showed convergent population-level associations with delay discounting impulsivity across group, correlational, and normative analyses.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712344","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":"Selected biomarkers of coagulation, inflammation, and vascular tone in young women with normal weight obesity","authors":"Waldemar Pluta,&nbsp;Anna Lubkowska,&nbsp;Wioleta Dudzińska","doi":"10.1038/s41366-026-02127-x","DOIUrl":"10.1038/s41366-026-02127-x","url":null,"abstract":"Individuals with the Normal Weight Obesity (NWO) phenotype are characterized by excessive body fat despite normal Body Mass Index (BMI), often leading to underestimated cardiovascular risk. The mechanisms linking this specific body composition to early vascular damage remain unclear. The aim of this study was to evaluate endothelial dysfunction biomarkers in young women with NWO, and to identify the main axes of vascular impairment. The study included 176 young women (median age 20) with normal BMI (18.5–24.9 kg/m²). Based on dual-energy X-ray absorptiometry (DXA), participants were classified into an NWO group (n = 88; percent body fat (PBF) ≥ 35.8%) and a healthy control group (NW; n = 88). Serum levels of tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), Angiopoietin-1 (Ang-1), Nitric Oxide (NO), and high-sensitivity C-reactive protein (hs-CRP) were analyzed. Principal Component Analysis (PCA) was employed to identify latent patterns of endothelial function. Women with NWO exhibited significantly higher levels of tPA (1.86 vs. 1.48 ng/ml; p = 0.038), vWF (72.24 vs. 63.62 ng/ml; p = 0.038), and Ang-1 (515.3 vs. 491.63 pg/ml; p = 0.008) compared to controls. PCA identified three principal components explaining 71.68% of the total variance: Coagulation (tPA, vWF), Inflammation/Angiogenesis (hs-CRP, Ang-1), and Vasodilation (NO). Young women with NWO exhibit subclinical endothelial dysfunction, which is characterized primarily by a pro-thrombotic state and disturbed angio-inflammatory balance. These changes occur even before the onset of overt metabolic or cardiovascular disease.","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":"50 9","pages":"2045-2051"},"PeriodicalIF":5.4,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41366-026-02127-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}