Unknown

Dataset Information

0

Dual activation of the bile acid nuclear receptor FXR and G-protein-coupled receptor TGR5 protects mice against atherosclerosis.


ABSTRACT: Bile acid signaling is a critical regulator of glucose and energy metabolism, mainly through the nuclear receptor FXR and the G protein-coupled receptor TGR. The purpose of the present study was to investigate whether dual activation of FXR and TGR5 plays a significant role in the prevention of atherosclerosis progression. To evaluate the effects of bile acid signaling in atherogenesis, ApoE-/- mice and LDLR-/- mice were treated with an FXR/TGR5 dual agonist (INT-767). INT-767 treatment drastically reduced serum cholesterol levels. INT-767 treatment significantly reduced atherosclerotic plaque formation in both ApoE-/- and LDLR-/- mice. INT-767 decreased the expression of pro-inflammatory cytokines and chemokines in the aortas of ApoE-/- mice through the inactivation of NF-?B. In addition, J774 macrophages treated with INT-767 had significantly lower levels of active NF-?B, resulting in cytokine production in response to LPS through a PKA dependent mechanism. This study demonstrates that concurrent activation of FXR and TGR5 attenuates atherosclerosis by reducing both circulating lipids and inflammation.

SUBMITTER: Miyazaki-Anzai S 

PROVIDER: S-EPMC4169583 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications

Dual activation of the bile acid nuclear receptor FXR and G-protein-coupled receptor TGR5 protects mice against atherosclerosis.

Miyazaki-Anzai Shinobu S   Masuda Masashi M   Levi Moshe M   Keenan Audrey L AL   Miyazaki Makoto M  

PloS one 20140919 9


Bile acid signaling is a critical regulator of glucose and energy metabolism, mainly through the nuclear receptor FXR and the G protein-coupled receptor TGR. The purpose of the present study was to investigate whether dual activation of FXR and TGR5 plays a significant role in the prevention of atherosclerosis progression. To evaluate the effects of bile acid signaling in atherogenesis, ApoE-/- mice and LDLR-/- mice were treated with an FXR/TGR5 dual agonist (INT-767). INT-767 treatment drastica  ...[more]

Similar Datasets

| S-EPMC8080777 | biostudies-literature
| S-EPMC3100601 | biostudies-literature
| S-EPMC2431107 | biostudies-literature
| S-EPMC5519354 | biostudies-literature
| S-EPMC3117992 | biostudies-literature
| S-EPMC6218869 | biostudies-literature
| S-EPMC7067245 | biostudies-literature
| S-EPMC5589588 | biostudies-literature
| S-EPMC4274506 | biostudies-literature
2019-11-19 | GSE139075 | GEO