RGD Reference Report - Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR. - Rat Genome Database

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Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR.

Authors: Ou, J  Tu, H  Shan, B  Luk, A  DeBose-Boyd, RA  Bashmakov, Y  Goldstein, JL  Brown, MS 
Citation: Ou J, etal., Proc Natl Acad Sci U S A 2001 May 22;98(11):6027-32.
RGD ID: 68702
Web Url: http://www.pnas.org/cgi/content/abstract/98/11/6027
Pubmed: PMID:11371634   (View Abstract at PubMed)
PMCID: PMC33416   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.111138698   (Journal Full-text)

Sterol regulatory element-binding protein-1c (SREBP-1c) enhances transcription of genes encoding enzymes of unsaturated fatty acid biosynthesis in liver. SREBP-1c mRNA is known to increase when cells are treated with agonists of liver X receptor (LXR), a nuclear hormone receptor, and to decrease when cells are treated with unsaturated fatty acids, the end products of SREBP-1c action. Here we show that unsaturated fatty acids lower SREBP-1c mRNA levels in part by antagonizing the actions of LXR. In cultured rat hepatoma cells, arachidonic acid and other fatty acids competitively inhibited activation of the endogenous SREBP-1c gene by an LXR ligand. Arachidonate also blocked the activation of a synthetic LXR-dependent promoter in transfected human embryonic kidney-293 cells. In vitro, arachidonate and other unsaturated fatty acids competitively blocked activation of LXR, as reflected by a fluorescence polarization assay that measures ligand-dependent binding of LXR to a peptide derived from a coactivator. These data offer a potential mechanism that partially explains the long-known ability of dietary unsaturated fatty acids to decrease the synthesis and secretion of fatty acids and triglycerides in livers of humans and other animals.



Gene Srebf1 sterol regulatory element binding transcription factor 1 Rattus norvegicus