Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor

Martin Göttlicher, Eva Widmark, Qiao Li, Jan Åke Gustafsson

Research output: Contribution to journalArticle

781 Scopus citations

Abstract

Peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643 have been shown to activate PPAR (peroxisome proliferator-activated receptor), a member of the steroid nuclear receptor superfamily. We have cloned the cDNA from the rat that is homologous to that from the mouse [Issemann, I. & Green, S. (1990) Nature (London) 347, 645-650], which encodes a 97% similar protein with a particularly well-conserved putative ligand-binding domain. To search for physiologically occurring activators, we established a transcriptional transactivation assay by stably expressing in CHO cells a chimera of rat PPAR and the human glucocorticoid receptor that activates expression of the placental alkaline phosphatase reporter gene under the control of the mouse mammary tumor virus promoter. Testing of compounds related to lipid metabolism or peroxisomal proliferation revealed that 150 μM concentrations of arachidonic or linoleic acid but not of dehydroepiandrosterone, cholesterol, or 25-hydroxy-cholesterol, activate the receptor chimera. In addition, saturated fatty acids induce the reporter gene. Shortening the chain length to n = 6 or introduction of an ω-terminal carboxylic group abolished the activation potential of the fatty acid. In conclusion, the present results indicate that fatty acids can regulate gene expression mediated by a member of the steroid nuclear receptor superfamily.

Original languageEnglish (US)
Pages (from-to)4653-4657
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number10
DOIs
StatePublished - 1992

Keywords

  • Alkaline phosphatase
  • Arachidonic acid
  • Nuclear receptor superfamily
  • Peroxisomal proliferation
  • Transcription factors

ASJC Scopus subject areas

  • Genetics
  • General

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