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 acti ve, these lipids must first be absorbed by the intestine and transformed by metabolic enzymes before they are delivered to their sites of action in th e body. Ultimately, the lipids must be eliminated to maintain a normal phys iological state. The need to coordinate this entire lipid-based metabolic s ignaling cascade raises important questions regarding the mechanisms that g overn these pathways. Specifically, what is the nature of communication bet ween these bioactive lipids and their receptors, binding proteins, transpor ters, and metabolizing enzymes that links them physiologically and speaks t o a higher level of metabolic control? Some general principles that govern the actions of this class of bioactive lipids and their nuclear receptors a re considered here, and the scheme that emerges reveals a complex molecular script at work.