Chronic Aspartame Exposure Leading to Hypertension in Mice may be Related to the Activation of the Wnt/β-Catenin Signaling Pathway in the Hypothalamus.

Aspartame is a commonly used sweetener that is increasingly becoming the main source of sweetness in foods due to its low-calorie and high-sweetness characteristics. Excessive intake of aspartame can lead to the occurrence of cardiovascular metabolic diseases and metabolic syndrome, especially hypertension. However, research on the correlation between exposure to aspartame and the development of hypertension remains insufficient. The hypothalamus is the main site regulating blood pressure. Our study established a chronic aspartame exposure model by administering 50 mg/kg aspartame water, measured the blood pressure of 4-week-old mice, and analyzed hypothalamic transcriptomic changes through full-length transcriptome sequencing. The results showed that chronic aspartame exposure significantly increased blood pressure in mice (p < 0.05). Full-length transcriptome sequencing identified 630 differentially expressed transcripts between the control and aspartame groups, with enrichment analysis showing significant changes in terms and pathways related to nervous system development and blood pressure. In addition, we found that increased neuronal necrosis in the paraventricular nucleus of the hypothalamus, and the Wnt/β-catenin signaling pathway was significantly activated in the aspartame group. In summary, our study suggested that chronic aspartame exposure is associated with elevated blood pressure in mice and affects the development of the hypothalamus at the transcript level.