Capsaicin Improves Glucose Tolerance and Insulin Sensitivity Through Modulation of the Gut Microbiota-Bile Acid-FXR Axis in Type 2 Diabetic db/db Mice
Capsaicin Improves Glucose Tolerance and Insulin Sensitivity Through Modulation of the Gut Microbiota-Bile Acid-FXR Axis in Type 2 Diabetic db/db Mice
复制标题
辣椒素通过调节 2 型糖尿病 db/db 小鼠的肠道微生物群-胆汁酸-FXR 轴来改善葡萄糖耐量和胰岛素敏感性
DOI：
10.1002/mnfr.201900608
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发表时间：
2019-12-01
影响因子：
5.2
通讯作者：
Mi, Mantian
中科院分区：
文献类型：
--
作者：
Hui, Suocheng;Liu, Yang;Mi, Mantian
范围 先前的研究已将膳食辣椒素 (CAP) 摄入量与改善葡萄糖稳态和胰岛素敏感性联系起来。然而，其根本机制仍不清楚。方法和结果 2 型糖尿病 db/db 小鼠接受饲料喂养，联合或不联合 CAP 治疗 8 周。 CAP 通过减少肝脏中的糖异生和增加糖原合成来显着改善葡萄糖耐量和胰岛素敏感性。此外，与食物喂养的小鼠水平相比，CAP 抑制乳杆菌属丰度及其胆汁盐水解酶 (BSH) 活性的增加，从而导致牛磺-β-鼠胆酸 (T beta MCA) 的积累，牛磺-β-鼠胆酸 (T beta MCA) 是法尼醇 X 受体 (FXR) 的天然拮抗剂，参与 BA 和葡萄糖代谢的调节。 CAP 诱导的肠肝 FXR 成纤维细胞生长因子 15 (FGF15) 信号传导抑制导致 BA 池大小增加，随后胆固醇 7 α-羟化酶 (CYP7A1) 的表达和肝脏 BA 合成增加。此外，通过施用抗生素来消耗肠道微生物群会消除 CAP 对 BA 代谢和葡萄糖稳态的有益影响。结论 db/db 小鼠中 CAP 诱导的 BA 和葡萄糖代谢改善部分是由肠道微生物群 - BA - 肠肝 FXR 轴介导的。
Scope Previous studies have linked dietary capsaicin (CAP) intake to improved glucose homeostasis and insulin sensitivity. However, the underlying mechanisms remain unclear. Methods and results Type 2 diabetic db/db mice are fed a chow diet with or without CAP treatment for 8 weeks. CAP administration markedly improves glucose tolerance and insulin sensitivity through decreasing gluconeogenesis and increasing glycogen synthesis in the liver. Furthermore, CAP inhibits the increase in abundance of the genus Lactobacillus and its bile salt hydrolase (BSH) activity compared with levels in chow-fed mice, thereby leading to the accumulation of tauro-beta-muricholic acid (T beta MCA), a natural antagonist of the farnesoid X receptor (FXR) that is involved in the regulation of BA and glucose metabolism. CAP-induced suppression of enterohepatic FXR-fibroblast growth factor 15 (FGF15) signaling contributes to the increased BA pool size, followed by increases in the expression of cholesterol 7 alpha-hydroxylase (CYP7A1) and hepatic BA synthesis. Additionally, depleting gut microbiota by antibiotics administration abolishes the beneficial effects of CAP on BA metabolism and glucose homeostasis. Conclusions CAP-induced improvements in BA and glucose metabolism are partially mediated by the gut microbiota-BA-enterohepatic FXR axis in db/db mice.