{"title":"Prospective associations of obesity heterogeneity, serum proteins, and carotid atherosclerosis risk.","authors":"Haili Zhong, Jieteng Chen, Shize Jia, Hanzu Chen, Yue Xi, Yan Yan, Zilong Lu, Congmei Xiao, Fengzhe Xu, Jun Tang, Ju-Sheng Zheng, Yu-Ming Chen","doi":"10.1016/j.ebiom.2025.105935","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Obese individuals exhibit considerable heterogeneity in developing cardiovascular diseases, yet the underlying molecular mechanisms remain unclear. We aimed to investigate the prospective associations between obesity phenotypes, serum proteomics, and carotid atherosclerosis (CAS) incidence.</p><p><strong>Methods: </strong>This cohort study included 3162 participants from the Guangzhou Nutrition and Health Study, with 413 proteins profiled from 6803 serum samples collected at three time-points. Obesity phenotypes included metabolically healthy non-obesity (MHNO) and metabolically healthy/unhealthy obesity (MHO/MUO).</p><p><strong>Findings: </strong>We identified 11 proteins influenced by MUO (vs. MHO) over time, with their combined score positively associated with incident CAS (HR: 1.16; 95% CI: 1.01-1.34). Additionally, 8 proteins were prospectively associated with MHO-to-MUO transition, which increased the performance of traditional risk factors in predicting this transition (P < 0.001). Among the 8 proteins, bidirectional mediation effects were observed between pigment epithelium-derived factor (PEDF) (36.8%; P = 0.025) and the MHO-to-MUO transition (20.5%; P = 0.010) on CAS incidence. The PEDF genetic risk score was positively associated with MHO-to-MUO transition (OR: 1.20; 95% CI: 1.00-1.43). Our main findings were validated in both the internal and external validation cohorts.</p><p><strong>Interpretation: </strong>This population-scale proteomics study broadens our understanding of the mechanisms underlying obesity heterogeneity and CAS, providing potential targets for the prevention of CAS.</p><p><strong>Funding: </strong>This study was supported by the National Natural Science Foundation of China, the Key Research and Development Program of Guangzhou, \"Pioneer\" and \"Leading goose\" R&D Program of Zhejiang, and the 5010 Program for Clinical Researches of the Sun Yat-sen University.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"120 ","pages":"105935"},"PeriodicalIF":10.8000,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EBioMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ebiom.2025.105935","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Obese individuals exhibit considerable heterogeneity in developing cardiovascular diseases, yet the underlying molecular mechanisms remain unclear. We aimed to investigate the prospective associations between obesity phenotypes, serum proteomics, and carotid atherosclerosis (CAS) incidence.
Methods: This cohort study included 3162 participants from the Guangzhou Nutrition and Health Study, with 413 proteins profiled from 6803 serum samples collected at three time-points. Obesity phenotypes included metabolically healthy non-obesity (MHNO) and metabolically healthy/unhealthy obesity (MHO/MUO).
Findings: We identified 11 proteins influenced by MUO (vs. MHO) over time, with their combined score positively associated with incident CAS (HR: 1.16; 95% CI: 1.01-1.34). Additionally, 8 proteins were prospectively associated with MHO-to-MUO transition, which increased the performance of traditional risk factors in predicting this transition (P < 0.001). Among the 8 proteins, bidirectional mediation effects were observed between pigment epithelium-derived factor (PEDF) (36.8%; P = 0.025) and the MHO-to-MUO transition (20.5%; P = 0.010) on CAS incidence. The PEDF genetic risk score was positively associated with MHO-to-MUO transition (OR: 1.20; 95% CI: 1.00-1.43). Our main findings were validated in both the internal and external validation cohorts.
Interpretation: This population-scale proteomics study broadens our understanding of the mechanisms underlying obesity heterogeneity and CAS, providing potential targets for the prevention of CAS.
Funding: This study was supported by the National Natural Science Foundation of China, the Key Research and Development Program of Guangzhou, "Pioneer" and "Leading goose" R&D Program of Zhejiang, and the 5010 Program for Clinical Researches of the Sun Yat-sen University.
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍:
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.