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The effect of FXR ligands on fatty liver model of cultured cells
Author(s) -
Miyazaki Teruo,
Honda Akira,
Ikegami Tadashi,
Shirai Mutsumi,
Matsuzaki Yasushi
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.534.5
Background/Aim Fatty acid synthesis is regulated by the LXR‐SREBP‐1c pathway, and this pathway is inactivated by FXR activation via SHP. This study aimed to establish a fatty liver model in cell lines by LXR ligand, and to examine the inhibitive effects of endogenous (bile acid) and synthetic FXR ligands on cellular triglyceride (TG) level. Methods Mice AML12 and Human HepG2 cells were exposed to either endogenous (oxysterols; 4βOH, 22ROH, 25OH, 24S,25‐Epoxy, 7αOH) or synthetic ( To901317 ) LXR‐ligands for a week. Furthermore, the cells were treated with FXR ligands (CDCA, GW4064) or non‐FXR ligand (UDCA) together with or post to To901317 exposure. The cellular TG level was evaluated by Oil‐red stain and TG assay as well as mRNA expressions of LXR target genes. Results Exposing to 10μƒÊM oxysterols (22ROH, 24S,25‐Epoxy) and 1μM To901317 significantly induced cellular TG accumulation with significantly increased mRNA expressions of SREBP‐1c, acetyl‐CoA carboxylase, fatty acid synthase, and steatory‐CoA desasturase‐1. In both cells, TG levels were significantly inhibited by treatment with 1–50μM CDCA or 1μM GW4064 together with and post to To901317, while there was no effect in UDCA. Discussion The treatment of FXR‐ligands inhibited both synthesis and catabolism of cellular TG in fatty liver model of cultured cells. Therefore, there is a possibility that FXR‐ligands might be therapeutic agents for fatty liver.