背景:岩藻依聚糖(FUC)的治疗潜力,一种天然多糖,在代谢紊乱是公认的,然而其潜在机制仍不清楚。
方法:我们对由高蔗糖饮食(HSD)引起的代谢紊乱的来自马尾藻的FUC的治疗机制进行了研究,采用果蝇和小鼠模型。对果蝇幼虫进行HSD暴露以监测生长抑制,减少化脓,和发育迟缓。此外,我们研究了FUC对果蝇生长和发育相关激素的影响。此外,我们评估了FUC对幼虫肠道稳态的调节,重点是Notch信号的调节。在老鼠身上,我们评估了FUC对HSD诱导的肠上皮屏障完整性和肠激素分泌损伤的影响。
结果:补充FUC可显着提高果蝇幼虫的p重量,并有效对抗HSD诱导的葡萄糖和甘油三酯水平升高。它特别影响了生长和发育相关激素的表达,特别是增加胰岛素样肽的产生,同时减轻幼虫生长迟缓。FUC还通过负调节Notch信号调节幼虫肠道稳态,从而防止HSD诱导的代谢应激。在老鼠身上,FUC改善了HSD诱导的回肠上皮屏障完整性和肠激素分泌的损伤。
结论:我们的研究结果证明了FUC在减轻代谢紊乱和维持肠道健康方面的多方面治疗作用。FUC作为治疗剂有希望,其作用部分归因于硫酸基团及其调节Notch信号传导的能力,强调其解决代谢紊乱的潜力。
BACKGROUND: The therapeutic potential of fucoidan (FUC), a natural polysaccharide, in metabolic disorders is recognized, yet its underlying mechanisms remain unclear.
METHODS: We conducted investigations into the therapeutic mechanisms of FUC sourced from Sargassum fulvellum concerning metabolic disorders induced by a high-sucrose diet (HSD), employing Drosophila melanogaster and mice models. Drosophila larvae were subjected to HSD exposure to monitor growth inhibition, reduced pupation, and developmental delays. Additionally, we examined the impact of FUC on growth- and development-related hormones in Drosophila. Furthermore, we assessed the modulation of larval intestinal homeostasis by FUC, focusing on the regulation of Notch signaling. In mice, we evaluated the effects of FUC on HSD-induced impairments in intestinal epithelial barrier integrity and gut hormone secretion.
RESULTS: FUC supplementation significantly enhanced pupal weight in Drosophila larvae and effectively countered HSD-induced elevation of glucose and triglyceride levels. It notably influenced the expression of growth- and development-related hormones, particularly augmenting insulin-like peptides production while mitigating larval growth retardation. FUC also modulated larval intestinal homeostasis by negatively regulating Notch signaling, thereby protecting against HSD-induced metabolic stress. In mice, FUC ameliorated HSD-induced impairments in ileum epithelial barrier integrity and gut hormone secretion.
CONCLUSIONS: Our findings demonstrate the multifaceted therapeutic effects of FUC in mitigating metabolic disorders and maintaining intestinal health. FUC holds promise as a therapeutic agent, with its effects attributed partly to the sulfate group and its ability to regulate Notch signaling, emphasizing its potential for addressing metabolic disorders.