Investigating the Potential Molecular Mechanisms of Mogroside V on Glucose Homeostasis by Transcriptome Profiling of Adult Mouse Hypothalamic Cells

Background: Mogroside V (MV), a natural sweetener extracted from monk fruit, has recently attracted growing interest due to its anti-inflammatory, antioxidant, and glucose metabolism-modulating properties. However, the transcriptomic effects of MV, especially in the context of glucose conditions, remain largely unexplored. This study aims to elucidate the impact of different MV concentrations on gene expression in hypothalamic neuronal cells under both normal and high glucose environments. Methods: Adult mouse hypothalamus neuronal cells were cultured under normal and high glucose conditions and treated with three MV concentrations (15 µM, 60 µM, and 160 µM). RNA sequencing was performed to assess transcriptomic changes. Differential gene expression analysis and functional pathway enrichment were conducted to identify biological processes and signaling pathways influenced by MV. Results: MV induced differential expression of up to 103 genes, depending on the dose and glucose context. Pathway analysis revealed activation of Notch and FoxO signaling, both implicated in glucose regulation, as well as the AMPK signaling pathway, which is critical for cellular energy homeostasis. MV also enriched pathways related to oxidative stress, aligning with its proposed antioxidant effects. Importantly, dose-dependent transcriptomic responses were observed under normal glucose conditions, but these effects were attenuated in high glucose settings, suggesting context-specific efficacy. Conclusions: MV exerts a dose-dependent influence on gene expression in hypothalamic neurons, particularly in pathways linked to glucose metabolism and oxidative stress. These findings underscore its potential as a metabolic modulator, warranting further investigation in animal models to assess its therapeutic relevance.