Transcriptomic evidence of hypothalamic neuroinflammation in mice due to aspartame exposure through the TLR4/NF-κB/NLRP3 pathway

The use of aspartame (ASP) instead of sugar is increasing. ASP exposure has been shown to affect the hypothalamus. However, whether it causes hypothalamic inflammation in mice and the specific molecular mechanisms are unknown. Here, we established an ASP exposure model with a body-weight-adjusted dose of 50 mg kg^-1 and employed Oxford Nanopore Technologies to investigate the differences in genes in the mice's hypothalamus. 491 differentially expressed genes were identified in the ASP group when compared with the control group. Functional enrichment analysis found that several terms and pathways related to immune function were altered in the hypothalamus. Furthermore, western blot outcomes showed that the TLR4/NF-κB/NLRP3 pathway was up-regulated. Immunofluorescence and enzyme-linked immunosorbent assay outcomes also suggested that the concentration of inflammatory factors increased. In conclusion, our results indicated that ASP exposure can induce inflammation in the hypothalamus tissue of mice and impair hypothalamic function in mice.