Adopting new orphans into the family of metabolic regulators

The importance of the adopted metabolite receptors, such as peroxisome proliferator-activated receptor, liver X receptor, and farnesoid X receptor, in transcriptional control of metabolic pathways has been appreciated for many years. However, it is becoming increasingly clear that the number of nuclear receptors with roles in metabolism is much larger than initially suspected. Recent years have brought an intense effort define the biological functions of the most enigmatic group of the nuclear receptor superfamily, the true orphan receptors, including nuclear receptor 4As, estrogen- related receptors, retinoidrelated orphan receptors, and Rev- erbs. Unexpectedly, several of these receptors also turn out to have important functions in various aspects of metabolic control.