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Chawla et al - Nuclear Receptors and Lipid Physiology...

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DOI: 10.1126/science.294.5548.1866 , 1866 (2001); 294 Science et al. Ajay Chawla, the X-Files Nuclear Receptors and Lipid Physiology: Opening www.sciencemag.org (this information is current as of January 7, 2008 ): The following resources related to this article are available online at http://www.sciencemag.org/cgi/content/full/294/5548/1866 version of this article at: including high-resolution figures, can be found in the online Updated information and services, http://www.sciencemag.org/cgi/content/full/294/5548/1866#otherarticles , 13 of which can be accessed for free: cites 26 articles This article 549 article(s) on the ISI Web of Science. cited by This article has been http://www.sciencemag.org/cgi/content/full/294/5548/1866#otherarticles 97 articles hosted by HighWire Press; see: cited by This article has been http://www.sciencemag.org/cgi/collection/cell_biol Cell Biology : subject collections This article appears in the following http://www.sciencemag.org/about/permissions.dtl in whole or in part can be found at: this article permission to reproduce of this article or about obtaining reprints Information about obtaining registered trademark of AAAS. is a Science 2001 by the American Association for the Advancement of Science; all rights reserved. The title Copyright American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the Science on January 7, 2008 www.sciencemag.org Downloaded from
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Nuclear Receptors and Lipid Physiology: Opening the X-Files Ajay Chawla, 1 * Joyce J. Repa, 2 * Ronald M. Evans, 1 ² David J. Mangelsdorf 2 ² Cholesterol, fatty acids, fat-soluble vitamins, and other lipids present in our diets are not only nutritionally important but serve as precursors for ligands that bind to receptors in the nucleus. To become biologically active, these lipids must first be absorbed by the intestine and trans- formed by metabolic enzymes before they are delivered to their sites of action in the body. Ultimately, the lipids must be eliminated to maintain a normal physiological state. The need to coordinate this entire lipid-based metabolic signaling cascade raises important questions regarding the mechanisms that govern these pathways. Specifically, what is the nature of communication between these bioactive lipids and their receptors, binding proteins, transporters, and metabolizing enzymes that links them physiologically and speaks to a higher level of metabolic control? Some general principles that govern the actions of this class of bioactive lipids and their nuclear receptors are considered here, and the scheme that emerges reveals a complex molecular script at work. Nuclear receptors function as ligand- activated transcription factors that regulate the expression of target genes to affect processes as diverse as reproduction, devel- opment, and general metabolism. These proteins were first recognized as the medi- ators of steroid hormone signaling and pro- vided an important link between transcrip- tional regulation and physiology. In the mid-1980s,
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