| First Author | Lambert G | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 4 | Pages | 2563-70 |
| PubMed ID | 12421815 | Mgi Jnum | J:81724 |
| Mgi Id | MGI:2449876 | Doi | 10.1074/jbc.M209525200 |
| Citation | Lambert G, et al. (2003) The Farnesoid X-receptor Is an Essential Regulator of Cholesterol Homeostasis. J Biol Chem 278(4):2563-70 |
| abstractText | To address the importance of the farnesoid X-receptor (FXR; NR1H4) for normal cholesterol homeostasis, we evaluated the major pathways of cholesterol metabolism in the FXR-deficient (-/-) mouse model. Compared with wild-type, FXR(-/-) mice have increased plasma high density lipoprotein (HDL) cholesterol and a markedly reduced rate of plasma HDL cholesterol ester clearance. Concomitantly, FXR(-/-) mice exhibit reduced expression of hepatic genes involved in reverse cholesterol transport, most notably, that for scavenger receptor BI. FXR(-/-) mice also have increased: (i) plasma non-HDL cholesterol and triglyceride levels, (ii) apolipoprotein B-containing lipoprotein synthesis, and (iii) intestinal cholesterol absorption. Surprisingly, biliary cholesterol elimination was increased in FXR(-/-) mice, despite decreased expression of hepatic genes thought to be involved in this process. These data demonstrate that FXR is a critical regulator of normal cholesterol metabolism and that genetic changes affecting FXR function have the potential to be pro-atherogenic. |
