Capsaicin improves glucose homeostasis by enhancing glucagon-like peptide-1 secretion through the regulation of bile acid metabolism via the remodeling of the gut microbiota in male mice
Capsaicin improves glucose homeostasis by enhancing glucagon-like peptide-1 secretion through the regulation of bile acid metabolism via the remodeling of the gut microbiota in male mice
复制标题
辣椒素通过重塑雄性小鼠肠道微生物群来调节胆汁酸代谢，从而增强胰高血糖素样肽-1 的分泌，从而改善葡萄糖稳态
DOI：
10.1096/fj.201902618rr
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发表时间：
2020-05-02
期刊：
影响因子：
4.8
通讯作者：
Mi, Mantian
中科院分区：
文献类型：
--
作者：
Hui, Suocheng;Huang, Li;Mi, Mantian
越来越多的证据表明，饮食中辣椒素（CAP）的消费与葡萄糖稳态的改善有关;然而，其潜在机制仍需进一步阐明。给雄性小鼠喂食高脂饮食（HFD）并给予CAP 8周，研究肠道微生物群、胆汁酸（BA）谱和BA标志物以及葡萄糖代谢。CAP部分通过促进胰高血糖素样肽1（GLP-1）的分泌来改善葡萄糖稳态。肠道微生物群被CAP重塑，其特征在于与石胆酸（LCA）产生相关的拟杆菌属丰度增加。LCA是Takeda G蛋白偶联受体5（TGR 5）的内源性激动剂;可增强肠道L细胞中GLP-1的分泌。同时，抗生素实验消除了CAP对葡萄糖稳态的影响，微生物群移植实验证明CAP诱导的有益作用是可传递的，表明CAP对葡萄糖稳态的影响在很大程度上依赖于肠道微生物群。此外，我们进一步确定CAP诱导的改善被GLP-1受体拮抗剂减弱，表明GLP-1信号传导的激活有助于CAP诱导的葡萄糖稳态改善。
Mounting evidence has linked dietary capsaicin (CAP) consumption to the improvement of glucose homeostasis; however, the underlying mechanisms still need to be further elucidated. Male mice were fed a high-fat diet (HFD) with CAP administration for 8 weeks, gut microbiota, bile acid (BA) profiles and markers for BA, and glucose metabolism were investigated. CAP improved glucose homeostasis partially by enhancing the secretion of glucagon-like peptide 1 (GLP-1). The gut microbiota was remodeled by CAP and was characterized by the increased abundance of Bacteroides genera, which is related with lithocholic acid (LCA) production. LCA is an endogenous agonist of Takeda G-protein coupled receptor 5 (TGR5); it may enhance GLP-1 secretion in intestinal L cells. Meanwhile, antibiotics experiment abolished the effects of CAP on glucose homeostasis and microbiota transplantation experiments demonstrated that the CAP-induced beneficial effects were transferable, indicating that the effects of CAP on glucose homeostasis were largely dependent on the gut microbiota. Additionally, we further identified that the improvements induced by CAP were attenuated by the antagonist of GLP-1 receptor, indicating that the activation of GLP-1 signaling contributes to the CAP-induced improvement in glucose homeostasis.