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Fucosterol, a liver X receptors agonist, stimulates RCT and regulates the expression of key genes in cholesterol homeostasis in vitro
Author(s) -
Hien Hoang Minh,
Lee SungJoon
Publication year - 2013
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.27.1_supplement.1079.28
Subject(s) - liver x receptor , abcg1 , abca1 , reverse cholesterol transport , nuclear receptor , liver x receptor alpha , biology , agonist , cholesterol , downregulation and upregulation , sterol regulatory element binding protein , transcription factor , microbiology and biotechnology , chemistry , receptor , sterol , endocrinology , biochemistry , lipoprotein , gene , transporter
We investigated whether fucosterol,sterol riches in marine algae, could activate liver X receptors (LXRs) activity, the critical transcription factors in the reverse cholesterol transport. Fucosterol dose‐dependently stimulated the transcriptional activity of both LXR‐α and LXR‐β in a reporter gene assay, responses that were attenuated by the LXR antagonist As 2 O 3 . Fucosterol also activated coactivator recruitment in cell‐free time‐resolved fluorescence resonance energy transfer analysis. In THP‐1‐derived macrophages, it induced the transcriptional activation of ABCA1, ABCG1, and apoE, key genes in reverse cholesterol transport, and thereby significantly increased the efflux of cholesterol. Fucosterol also regulated intestinal NPC1L1 and ABCA1 in Caco‐2 cells. Notably, fucosterol did not induce cellular triglyceride accumulation in HepG2 cells, primarily due to its upregulation of Insig‐2a, which delays nuclear translocation of SREBP‐1c, a key hepatic lipogenic transcription factor. These results suggest that fucosterol is a dual‐LXR agonist that regulates the expression of key genes in cholesterol homeostasis in multiple cell lines without inducing hepatic triglyceride accumulation.