Mary Wilson
Well-known member
February 19, 2025
DOI: 10.1016/j.cmet.2025.01.006
Weijie Wu, Wenhai Sui, Sizhe Chen, ..., Yuguo Chen, Cheng Zhang, Yihai Cao
Highlights
Aspartame increases insulin levels through parasympathetic activation
•
An insulin-dependent mechanism of the aspartame-aggravated atherosclerosis
•
The CX3CL1-CX3CR1 signaling mediates insulin-induced endothelial inflammation
•
A CX3CL1-CX3CR1-dependent mechanism of aspartame-exacerbated atherosclerosis
Summary
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[SUP]−/[/SUP][SUP]−[/SUP]mice aggravated atherosclerotic plaque formation and growth via an insulin-dependent mechanism. Implantation of an insulin-slow-release pump in ApoE[SUP]−/−[/SUP] 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, Cx3cr1gene, 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.
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(25)00006-3
DOI: 10.1016/j.cmet.2025.01.006
Weijie Wu, Wenhai Sui, Sizhe Chen, ..., Yuguo Chen, Cheng Zhang, Yihai Cao
Highlights
Aspartame increases insulin levels through parasympathetic activation
•
An insulin-dependent mechanism of the aspartame-aggravated atherosclerosis
•
The CX3CL1-CX3CR1 signaling mediates insulin-induced endothelial inflammation
•
A CX3CL1-CX3CR1-dependent mechanism of aspartame-exacerbated atherosclerosis
Summary
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[SUP]−/[/SUP][SUP]−[/SUP]mice aggravated atherosclerotic plaque formation and growth via an insulin-dependent mechanism. Implantation of an insulin-slow-release pump in ApoE[SUP]−/−[/SUP] 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, Cx3cr1gene, 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.
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(25)00006-3