顶刊综述丨NAT REV MICROBIOL (IF:78): 胆汁酸和肠道微生物群: 代 …
2023年3月4日 · 两种fxr信号通路都抑制胆固醇7α-羟化酶(cyp7a1)和固醇12α-羟化酶(cyp8b1)的表达，这两种酶参与经典ba生物合成途径。 为了减轻BA毒性，FXR诱导BA-CoA:氨基酸N-酰基转移酶(BAAt)在肝脏的表达，从而抑制非结合BAs的积累。
FXR in liver physiology: Multiple faces to regulate liver metabolism
2021年7月1日 · FXR directly regulates CYP7A1, the rate limiting enzyme in the conversion of cholesterol into bile acids. This is probably the most crucial function of FXR because thereby it also controls - in a feedback loop - its own physiological ligand availability.
Hepatic FXR-FGF4 is required for bile acid homeostasis via an …
2024年10月10日 · We identified hepatic Fgf4 as a direct FXR target that paracrinally signals to downregulate Cyp7a1 and Cyp8b1. The effect of FXR-FGF4 is mediated by an uncharted intracellular FGF receptor 4 (FGFR4)-LRH-1 signaling node.
Cholesterol 7α-hydroxylase protects the liver from inflammation …
Cholesterol 7α-hydroxylase (CYP7A1) plays a critical role in control of bile acid and cholesterol homeostasis. Bile acids activate farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) to regulate lipid, glucose, and energy metabolism.
Up to date on cholesterol 7 alpha-hydroxylase (CYP7A1) in bile …
2020年6月1日 · FXR induces the negative co-repressor small heterodimer partner (SHP) to inhibit hepatocyte nuclear factor 4 alpha (HNF4α)/LXR-mediated activation of CYP7A1. FXR also activates bile salt export pump (BSEP) to efflux bile acids into gallbladder bile, and FXR inhibits sodium taurocholate co-transport peptide (NTCP), preventing the accumulation ...
FXR调控胆汁酸与糖脂代谢改善NAFLD的机制
2023年10月8日 · 肝脏中胆汁酸增多时, 肝FXR激活, 启动下游小分子异源二聚体(small heterodimer partner, SHP), 其一, 抑制CYP7A1(替代途径CYP27A1), 降低肝内胆固醇向初级胆汁酸的转化; 其二, 激活肝细胞中的胆盐输出泵[(bile salt export pump, BSEP), 或称ATP结合盒转运蛋白B11(ATP-binding cassette ...
Atorvastatin Induces FXR and CYP7A1 Activation as a Result of …
2021年3月25日 · Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.
An FGF15/19-TFEB regulatory loop controls hepatic cholesterol
2020年7月17日 · Intestinal FXR senses elevated bile acids to induce mouse fibroblast growth factor 15 (FGF15) (human ortholog FGF19), which acts as an endocrine hormone to feedback inhibit hepatic CYP7A1 gene...
A regulatory cascade of the nuclear receptors FXR, SHP-1, and …
SHP-1 represses expression of CYP7A1 by inhibiting the activity of liver receptor homolog 1 (LRH-1), an orphan nuclear receptor that is known to regulate CYP7A1 expression positively. This bile acid-activated regulatory cascade provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis.
Pharmacological modulation of cholesterol 7α-hydroxylase (CYP7A1…
2024年2月1日 · By employing FXR antagonists to block both FXR-mediated pathways, there is a likelihood that downstream CYP7A1 expression can be upregulated to increase the metabolism of cholesterol to bile acids and consequently attenuate cholesterol levels in the body.