Farnesoid X receptor up-regulates expression of lipid transfer inhibitor protein in liver cells and mice

Biochem Biophys Res Commun. 2013 Nov 29;441(4):880-5. doi: 10.1016/j.bbrc.2013.10.156. Epub 2013 Nov 6.

Abstract

Apolipoprotein F is a component protein mainly secreted by liver and resides on several lipoprotein classes. It can inhibit lipids transfer between different lipoproteins. FXR is a member of the nuclear receptor superfamily which is also highly expressed in the liver. It modulates bile acids synthesis and lipids metabolism by transcriptional regulation. We aimed to determine whether apoF can be regulated by FXR. The FXR agonist Chenodeoxycholic acid (CDCA) and GW4064 both can activate the expression of apoF in liver cell lines and in C57/BL6 mouse liver. This is dependent on the binding of FXR to the FXR element ER1 (-2904 to -2892 bp) in the apoF gene promoter. Taken together, we have identified apoF as likely another target gene of FXR.

Keywords: Apolipoprotein F; CETP; Chenodeoxycholic acid; Cholesterol ester transfer protein; FXR; High density lipoprotein; Low density lipoprotein; apoF; apolipoprotein F; cholesterol ester transfer protein; farnesoid X receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins / genetics*
  • Chenodeoxycholic Acid / pharmacology
  • Gene Expression Regulation
  • Hep G2 Cells
  • Humans
  • Isoxazoles / pharmacology
  • Liver / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Up-Regulation

Substances

  • Apolipoproteins
  • Isoxazoles
  • Receptors, Cytoplasmic and Nuclear
  • apolipoprotein F
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • GW 4064