214 0

Cinnamamides, Novel Liver X Receptor Antagonists that Inhibit Ligand-Induced Lipogenesis and Fatty Liver

Title
Cinnamamides, Novel Liver X Receptor Antagonists that Inhibit Ligand-Induced Lipogenesis and Fatty Liver
Author
전대원
Keywords
ELEMENT-BINDING PROTEIN-1C; CINNAMIC ACID-DERIVATIVES; LXR-ALPHA; NUCLEAR RECEPTORS; GENE-EXPRESSION; INSULIN-RESISTANCE; SREBP-1C; AGONIST; INFLAMMATION; STIMULATION
Issue Date
2015-11
Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Citation
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, v. 355, NO 3, Page. 362-369
Abstract
Liver X receptor (LXR) is a member of the nuclear receptor superfamily, and it regulates various biologic processes, including de novo lipogenesis, cholesterol metabolism, and inflammation. Selective inhibition of LXR may aid the treatment of nonalcoholic fatty liver diseases. In the present study, we evaluated the effects of three cinnamamide derivatives on ligand-induced LXR alpha activation and explored whether these derivatives could attenuate steatosis in mice. N-(4-trifluoromethylphenyl) 3,4-dimethoxycinnamamide (TFCA) decreased the luciferase activity in LXRE-tk-Luc-transfected cells and also suppressed ligand-induced lipid accumulation and expression of the lipogenic genes in murine hepatocytes. Furthermore, it significantly attenuated hepatic neutral lipid accumulation in a ligand-induced fatty liver mouse system. Modeling study indicated that TFCA inhibited activation of the LXR alpha ligand-binding domain by hydrogen bonding to Arg305 in the H5 region of that domain. It regulated the transcriptional control exerted by LXR alpha by influencing coregulator exchange; this process involves dissociation of the thyroid hormone receptor-associated proteins (TRAP)/DRIP coactivator and recruitment of the nuclear receptor corepressor. These results show that TFCA has the potential to attenuate ligand-induced lipogenesis and fatty liver by selectively inhibiting LXR alpha in the liver.
URI
http://jpet.aspetjournals.org/content/355/3/362http://hdl.handle.net/20.500.11754/28978
ISSN
0022-3565; 1521-0103
DOI
10.1124/jpet.115.226738
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE