Orphan Nuclear Receptors: An Emerging Family of Metabolic Regulators

Abstract

The search for ligands and functions associated with these putative receptors, referred to as orphan nuclear receptors, has become an active and rewarding field of research. The discovery that specific orphan nuclear receptors respond to nonclassical hormones, such as vitamin A derivatives, prostanoids, sterols, and fatty acids, combined with the observation that nuclear receptor response elements are present in the promoter regions of genes encoding enzymes involved in cellular metabolism, suggest that orphan nuclear receptors may be important regulators of basic cellular function in vivo. Orphan nuclear receptors are increasingly being identified as important regulators of genes encoding enzymes involved in cellular metabolism. Members of the nuclear receptor frequently bind to similar hormone response elements (HREs), suggesting that many novel receptors are likely to be linked to the metabolic functions through the characterization of factors regulating receptor expression, identification of receptor target and ligands, and careful characterization of metabolic pathways in receptor knockout mice. This chapter discusses such current knowledge on a subset of orphan nuclear receptors that have been identified as important regulators of these metabolic pathways. Findings suggest that many orphan nuclear receptors transduce intracellular signals essential for the regulation of basic cellular functions and modulate gene expression in response to environmental stimuli and metabolic demands.