| First Author | Zhang Y | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 5 | Pages | 3035-43 |
| PubMed ID | 19996107 | Mgi Jnum | J:159763 |
| Mgi Id | MGI:4452419 | Doi | 10.1074/jbc.M109.083899 |
| Citation | Zhang Y, et al. (2010) Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia. J Biol Chem 285(5):3035-43 |
| abstractText | Farnesoid X receptor (FXR) plays important regulatory roles in bile acid, lipoprotein, and glucose homeostasis. Here, we have utilized Fxr(-/-) mice and mice deficient in scavenger receptor class B type I (SR-BI), together with an FXR-specific agonist and adenovirus expressing hepatocyte nuclear factor 4alpha or constitutively active FXR, to identify the mechanisms by which activation of FXR results in hypocholesterolemia. We identify a novel pathway linking FXR to changes in hepatic p-JNK, hepatocyte nuclear factor 4alpha, and finally SR-BI. Importantly, we demonstrate that the FXR-dependent increase in SR-BI results in both hypocholesterolemia and an increase in reverse cholesterol transport, a process involving the transport of cholesterol from peripheral macrophages to the liver for excretion into the feces. In addition, we demonstrate that FXR activation also induces an SR-BI-independent increase in reverse cholesterol transport and reduces intestinal cholesterol absorption. Together, these data indicate that FXR is a promising therapeutic target for treatment of hypercholesterolemia and coronary heart disease. |
