Nuclear Receptors and Lipid Physiology: Opening the X-Files

作者：Ajay Chawla, Joyce J. Repa, Ronald M. Evans, David J. Mangelsdorf · 发表于：Science · 年份：2001 · DOI：10.1126/science.294.5548.1866 · 被引用次数：2096 · 研究领域：Cholesterol and Lipid Metabolism、Cancer, Lipids, and Metabolism、Peroxisome Proliferator-Activated Receptors

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. Nuclear receptors function as ligand-activated transcription factors that regulate the expression of target genes to affect processes as diverse as reproduction, development, and general metabolism. These proteins were first recognized as the mediators of steroid hormone signaling and provided an important link between transcriptional regulation and physiology. In the mid-1980s, the steroid receptors were cloned and found to exhi...