Nuclear receptors and lipid physiology: opening the X-files.
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.
Chawla
A
A
Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, Post Office Box 85800, San Diego, CA 92186-5800, USA.
Repa
J J
JJ
Evans
R M
RM
Mangelsdorf
D J
DJ
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism; D000090702:Constitutive Androstane Receptor; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000145:classification / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D047488:Retinoid X Receptors; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002784:Cholesterol; D000090702:Constitutive Androstane Receptor; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D015262:Xenobiotics; D000099150:Receptor, Farnesoid X-Activated