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Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Wu Weijie[1,2] * ; Sui Wenhai[1,2] ; Chen Sizhe[1,2] ; Guo Ziheng[3] ; Jing Xu[2] ; Wang Xiaolu[2] ; Wang Qun[2] ; Yu Xinshuang[2] ; Xiong Wenjing[1,2] ; Ji Jiansong[4] ; Yang Libo[5] ; Zhang Yuan[1] ; Jiang Wenjing[1] ; Yu Guohua[6] ; Liu Shuzhen[6] ; Tao Wei[7] ; Zhao Chen[8] ; Zhang Yun[1] ; Chen Yuguo[10] ; Zhang Cheng[1] ; Cao Yihai[2,9] ;
机构： [1]State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission, Chinese Academy of Medical Sciences and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China [2]Department of Microbiology, Tumor and Cell Biology, Hong Kong Centre for Cerebro-cardiovascular Health Engineering, Karolinska Institute, 171 65 Stockholm, Sweden [3]Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China [4]Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui 323000, China [5]Department of Endocrinology, The Affiliated Taian City Central Hospital of Qingdao University, Taian City, Shandong Province, China [6]Clinical Oncology Department, Weifang People’s Hospital, Kuiwen, Weifang, China [7]Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA [8]Eye Institute, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China [9]Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China [10]Department Nuclear Medicine, Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China
出处：
DOI： 10.1016/j.cmet.2025.01.006
ISSN：

摘要：
Consumption of artificial sweeteners (ASWs) in various foods and beverages has been linked to an increased risk of cardiovascular diseases (CVDs). However, molecular mechanisms underlying ASW-associated CVD remain unknown. Here, we show that consumption of 0.15% aspartame (APM) markedly increased insulin secretion in mice and monkeys. Bilateral subdiaphragmatic vagotomy (SDV) obliterated APM-elevated blood insulin levels, demonstrating crucial roles of parasympathetic activation in regulation of insulin secretion. Incessant APM feeding of ApoE-/- mice aggravated atherosclerotic plaque formation and growth via an insulin-dependent mechanism. Implantation of an insulin-slow-release pump in ApoE-/- mice exacerbated atherosclerosis. Whole-genome expression profiling discovered that CX3CL1 chemokine was the most upregulated gene in the insulin-stimulated arterial endothelial cells. Specific deletion of a CX3CL1 receptor, Cx3cr1 gene, in monocytes/macrophages completely abrogated the APM-exacerbated atherosclerosis. Our findings uncover a novel mechanism of APM-associated atherosclerosis and therapeutic targeting of the endothelial CX3CL1-macrophage CX3CR1 signaling axis provides an approach for treating atherosclerotic CVD.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

基金：
Y. Cao’s laboratory is supported through research grants from the Swedish Cancer Foundation, the Strategic Research Areas (SFO)–Stem Cell and Regenerative Medicine Foundation, the Karolinska Institute Foundation, the NOVO Nordisk Foundation, the Swedish Research Council (project no. 2016-02215, project no. 2019-01502, and project no. 2021-06122), the Swedish Research Council-the National Natural Science Foundation of China joint grants, the Hong Kong Centre for Cerebro-Cardiovascular Health Engineering, and the Horizon Europe grant-PERSEUS (action number: 101099423). State Key Laboratory for Innovation and Transformation of Luobing Theory is supported through research grants from Key R&D Program of Shandong Province (2021SFGC0503, 2021ZLGX02, 2021ZDSYS05), the National Natural Science Foundation of China (82241203, 82030051), State Key R&D Program of China (2021YFF0501403), and the Taishan Scholars Program of Shandong Province (to C. Zhang).
语种：
外文
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PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类 | 1 区 生物学
小类 | 1 区 细胞生物学 1 区 内分泌学与代谢
最新[2025]版：
大类 | 1 区 生物学
小类 | 1 区 细胞生物学 1 区 内分泌学与代谢
JCR分区：
出版当年[2024]版：
Q1 CELL BIOLOGY Q1 ENDOCRINOLOGY & METABOLISM
最新[2024]版：
Q1 CELL BIOLOGY Q1 ENDOCRINOLOGY & METABOLISM

影响因子： 最新[2024版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2024版]

第一作者：
第一作者机构： [1]State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission, Chinese Academy of Medical Sciences and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China [2]Department of Microbiology, Tumor and Cell Biology, Hong Kong Centre for Cerebro-cardiovascular Health Engineering, Karolinska Institute, 171 65 Stockholm, Sweden
通讯作者：
通讯机构： [2]Department of Microbiology, Tumor and Cell Biology, Hong Kong Centre for Cerebro-cardiovascular Health Engineering, Karolinska Institute, 171 65 Stockholm, Sweden [9]Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China
推荐引用方式(GB/T 7714)：
Wu Weijie,Sui Wenhai,Chen Sizhe,et al.Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation[J].Cell Metabolism.2025,37(5):doi:10.1016/j.cmet.2025.01.006.
APA：
Wu Weijie,Sui Wenhai,Chen Sizhe,Guo Ziheng,Jing Xu...&Cao Yihai.(2025).Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation.Cell Metabolism,37,(5)
MLA：
Wu Weijie,et al."Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation".Cell Metabolism 37..5(2025)

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