Prospective associations of obesity heterogeneity, serum proteins, and carotid atherosclerosis risk.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-10-01 Epub Date: 2025-09-20 DOI:10.1016/j.ebiom.2025.105935

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

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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.

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肥胖异质性、血清蛋白和颈动脉粥样硬化风险的前瞻性关联。

背景：肥胖个体在发生心血管疾病方面表现出相当大的异质性，但其潜在的分子机制尚不清楚。我们的目的是研究肥胖表型、血清蛋白质组学和颈动脉粥样硬化（CAS）发病率之间的前瞻性关联。方法：本队列研究包括来自广州营养与健康研究的3162名参与者，从三个时间点收集的6803份血清样本中分析了413种蛋白质。肥胖表型包括代谢健康的非肥胖（MHNO）和代谢健康/不健康的肥胖（MHO/MUO）。研究结果：我们确定了11种受MUO影响的蛋白（相对于MHO），它们的综合评分与CAS事件呈正相关（HR: 1.16; 95% CI: 1.01-1.34）。此外，有8种蛋白与MHO-to-MUO转变相关，这增加了传统危险因素在预测这种转变方面的表现（P < 0.001）。8种蛋白中，色素上皮衍生因子（PEDF）（36.8%, P = 0.025）和MHO-to-MUO转化（20.5%,P = 0.010）对CAS发病率有双向介导作用。PEDF遗传风险评分与mho - muo转换呈正相关（OR: 1.20; 95% CI: 1.00-1.43）。我们的主要发现在内部和外部验证队列中都得到了验证。这项人群规模的蛋白质组学研究拓宽了我们对肥胖异质性和CAS机制的理解，为预防CAS提供了潜在的靶点。基金资助：本研究得到国家自然科学基金、广州市重点研发计划、浙江省“先行者”和“领头鹅”研发计划、中山大学临床研究5010计划的支持。

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来源期刊

EBioMedicine Biochemistry, 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.