Docosahexaenoic Acid, a Ligand for the Retinoid X Receptor in Mouse Brain

• Published in: Science (American Association for the Advancement of Science) Vol. 290; no. 5499; pp. 2140 - 2144
• Main Authors: de Urquiza, Alexander Mata, Liu, Suya, Sjöberg, Maria, Zetterström, Rolf H., Griffiths, William, Sjövall, Jan, Perlmann, Thomas
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 15.12.2000; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Biochemistry; Biological and medical sciences; Biological Assay; Biotechnology industries; Biotechnology industry; Brain; Brain - growth & development; Brain - metabolism; Brain Chemistry; Cell Line; Cell physiology; Cells; Chromatography, High Pressure Liquid; Culture Media, Conditioned; Dimerization; docosahexaenoic acid; Docosahexaenoic Acids - isolation & purification; Docosahexaenoic Acids - metabolism; Docosahexaenoic Acids - pharmacology; Fatty acids; Fatty Acids, Unsaturated - pharmacology; Fractions; Fundamental and applied biological sciences. Psychology; Genes; Goods and services tax; Hexanes; Histone Acetyltransferases; Humans; Ligands; Ligands (Biochemistry); Male; Mass spectroscopy; Medicin och hälsovetenskap; Mice; Molecular and cellular biology; Monounsaturated fatty acids; Neural receptors; Nuclear Receptor Coactivator 1; Nuclear receptors; Omega 3 fatty acids; Receptors; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - metabolism; Recombinant Fusion Proteins - metabolism; Retinoid X Receptors; Retinoids; Rodents; Signal Transduction; Spectrometry, Mass, Electrospray Ionization; Tissues; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Tumor Cells, Cultured; Unsaturated fatty acids; Sweden; Signal transduction; Vertebrata; Mammalia; Mouse; Rodentia; Retinoid; Docosahexaenoic acid; Transcription factor; Mass spectrometry; Brain (vertebrata); Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.290.5499.2140

The retinoid X receptor (RXR) is a nuclear receptor that functions as a ligand-activated transcription factor. Little is known about the ligands that activate RXR in vivo. Here, we identified a factor in brain tissue from adult mice that activates RXR in cell-based assays. Purification and analysis of the factor by mass spectrometry revealed that it is docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid that is highly enriched in the adult mammalian brain. Previous work has shown that DHA is essential for brain maturation, and deficiency of DHA in both rodents and humans leads to impaired spatial learning and other abnormalities. These data suggest that DHA may influence neural function through activation of an RXR signaling pathway.