The farnesoid X receptor induces very low density lipoprotein receptor gene expression.
The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). In response to ligand-binding, FXR regulates many genes involved in BA, lipid, and lipoprotein metabolism. To identify new FXR target genes, microarray technology was used to profile total RNA extracted from HepG2 cells treated with the natural FXR agonist chenodeoxycholic acid (CDCA). Interestingly, a significant increase of transcript level of the very low density lipoprotein receptor (VLDLR) was observed. Our data, resulting from selective FXR activation, FXR RNA silencing and FXR-deficient mice, clearly demonstrate that BAs up-regulate VLDLR transcript levels via a FXR-dependent mechanism in vitro in human and in vivo in mouse liver cells.
Sirvent
Audrey
A
GENFIT, Parc Eurasanté, Loos, France.
Claudel
Thierry
T
Martin
Geneviève
G
Brozek
John
J
Kosykh
Vladimir
V
Darteil
Raphaël
R
Hum
Dean W
DW
Fruchart
Jean-Charles
JC
Staels
Bart
B
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D045744:Cell Line, Tumor; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D004268:DNA-Binding Proteins; D007555:Isoxazoles; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C036053:VLDL receptor; C412815:GW 4064