Regulation of metabolism by retinoic acid and its nuclear receptors

It is now well established that the pleiotropic effects of vitamin A-with the exception of the vision process-are mediated by its acid derivatives. Although all-trans retinoic acid has been known for some time to be an essential regulator for many important biological processes, critical roles for other acid derivatives have more recently emerged. The acid isoforms affect a large diversity of biological systems, including embryonal cells, lymphoid cells, and nerve and muscle cells, as well as essential developmental programs. Retinoic acid signals are mediated by specific nuclear receptors, the RARs and RXRs, which are part of a complex signaling network, allowing for receptor-receptor and receptor-DNA interaction, as well as for receptor interactions with other regulatory proteins. Dissection of the molecular mechanisms has been significantly advanced by the discovery of selective retinoids that in contrast to most natural retinoids activate only defined portions of the complex retinoid response. Some of these novel types of retinoids are also very promising candidates for the development of new therapeutics. Thus, the molecular analysis of the vitamin A derivative retinoic acid has opened new perspectives that form a connection between nutritional signals and the development of new therapeutic agents.