糖异生
胆汁酸
熊去氧胆酸
高脂血症
化学
脂肪变性
内科学
胆酸
内分泌学
新陈代谢
生物
生物化学
医学
糖尿病
作者
Kai Wang,Min Liao,Nan Zhou,Bao Li,Ke Ma,Zhongyong Zheng,Yujing Wang,Chang Liu,Wenzhao Wang,Jun Wang,Shuang‐Jiang Liu,Hongwei Liu
出处
期刊:Cell Reports
[Elsevier]
日期:2019-01-01
卷期号:26 (1): 222-235.e5
被引量:756
标识
DOI:10.1016/j.celrep.2018.12.028
摘要
We demonstrated the metabolic benefits of Parabacteroides distasonis (PD) on decreasing weight gain, hyperglycemia, and hepatic steatosis in ob/ob and high-fat diet (HFD)-fed mice. Treatment with live P. distasonis (LPD) dramatically altered the bile acid profile with elevated lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) and increased the level of succinate in the gut. In vitro cultivation of PD demonstrated its capacity to transform bile acids and production of succinate. Succinate supplementation in the diet decreased hyperglycemia in ob/ob mice via the activation of intestinal gluconeogenesis (IGN). Gavage with a mixture of LCA and UDCA reduced hyperlipidemia by activating the FXR pathway and repairing gut barrier integrity. Co-treatment with succinate and LCA/UDCA mirrored the benefits of LPD. The binding target of succinate was identified as fructose-1,6-bisphosphatase, the rate-limiting enzyme in IGN. The succinate and secondary bile acids produced by P. distasonis played key roles in the modulation of host metabolism.
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