Summary:
This is an animal study that investigated whether aspartame, a commonly used artificial sweetener, contributes to the development of atherosclerosis, a condition involving plaque build-up in arteries that increases the risk of cardiovascular disease. Previous research has linked artificial sweetener consumption to obesity, type 2 diabetes and cardiovascular disease, although findings have been inconsistent. This study focused on insulin, a hormone that regulates blood glucose levels. Elevated insulin levels and insulin resistance are recognised risk factors for cardiovascular disease. The study found that aspartame increased insulin secretion through activation of gut-brain signalling involving the vagus nerve. Higher insulin levels were associated with increased plaque formation in arteries, suggesting that insulin may play a key role in the development of atherosclerosis. Further analysis identified an inflammatory signalling pathway which promotes the recruitment of immune cells to blood vessel walls. Blocking this pathway prevented the worsening of atherosclerosis caused by aspartame exposure. Overall, this study suggests that aspartame may accelerate atherosclerosis through increased insulin secretion and activation of inflammatory pathways. These findings provide a potential mechanism linking artificial sweetener consumption with cardiovascular disease risk, however it is an animal study and not necessarily transferable to humans.
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Abstract:
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.
Article Publication Date: 06/05/2025
DOI: 10.1016/j.cmet.2025.01.006
