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FoxO1negatively regulates sterol regulatory element binding protein‐1c (SREBP‐1c) gene
Author(s) -
Deng Xiong,
Howell George,
Yellaturu Chandrahasa,
Wilcox Henry,
Park Edwards,
Raghow Rajendra,
Elam Marshall,
Unterman Terry
Publication year - 2009
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.23.1_supplement.660.16
Subject(s) - foxo1 , sterol regulatory element binding protein , transcription factor , liver x receptor , biology , promoter , reporter gene , response element , chemistry , endocrinology , medicine , microbiology and biotechnology , gene expression , nuclear receptor , gene , biochemistry
The induction of genes involved in lipid biosynthesis by insulin is mediated in part by the sterol regulatory element‐binding protein‐1c (SREBP‐1c) and this effect is mediated in part through a mechanism that is dependent on the liver X receptor alpha (LXRα). FoxO1, a forkhead box class‐O transcription factor, is an important target of insulin action. We performed experiments to study the effects of FoxO1 on SREBP‐1c gene expression. Our studies show that over‐expression of constitutively active FoxO1 protein (CA‐FoxO1) inhibits, and small interference RNA against FoxO1 enhances both basal and insulin‐stimulated activity of the rat SREBP‐1c promoter. CA‐FoxO1 suppresses the activities of the SREBP‐1c promoter in a dose‐dependent fashion, and antagonizes the effect of insulin and TO901317 (a synthetic ligand of LXRα) on promoter activity. CA‐FoxO1 significantly reduces the effect of LXRα ?on basal and TO901317‐stimulated activity of a luciferase reporter construct driven by 3 LXR‐response elements, and decreases the transactivational ability of a Gal4‐LXRα fusion protein. These results indicate that FoxO1 plays an important role in regulating basal and insulin‐stimulated SREBP‐1c promoter activity and may exert this effect by antagonizing the function of LXRα. This work was supported by a grant from the Office of Research and Development, Department of Veterans Affairs.