Nuclear Receptors and Lipid Physiology: Opening the X-Files

• Published in: Science (American Association for the Advancement of Science) Vol. 294; no. 5548; pp. 1866 - 1870
• Main Authors: Chawla, Ajay, Repa, Joyce J., Evans, Ronald M., Mangelsdorf, David J.
• Format: Journal Article
• Language: English
• Published: United States American Society for the Advancement of Science 30.11.2001; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Bile acids; Bile Acids and Salts - metabolism; Cell receptors; Cells; Cellular biology; Cholesterol - analogs & derivatives; Cholesterol - metabolism; Dimerization; DNA-Binding Proteins - metabolism; Enzymes; Fatty acids; Fatty Acids - metabolism; Gene expression regulation; Humans; Individualized Instruction; Ligands; Lipid Metabolism; Lipids; Liver X Receptors; Metabolism; Molecules; Nuclear receptors; Obesity; Orphan Nuclear Receptors; Physiological aspects; Physiology; Receptors; Receptors, Cytoplasmic and Nuclear - classification; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Retinoic Acid - metabolism; Receptors, Steroid - metabolism; Retinoid X Receptors; Reviews and Viewpoints; Signal Transduction; Transcription Factors - metabolism; Xenobiotics; Xenobiotics - metabolism; Zoology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.294.5548.1866

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 transformed 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.