Lipid-activated nuclear receptors: from gene transcription to the control of cellular metabolism

Cellular homeostasis is maintained through a complicated network of signaling, trans port and enzymatic events that take place in different compartments of the cell. The result of this composite network determines the cellular behavior in response to environmental challenges. Within this network, many cellular functions are regulated at the transcriptional level and consequently the comprehension of the molecular mechanisms of gene regulation is fundamental to fully understand how the cell reacts to environmental changes. Moreover, it offers an opportunity to find novel targets for the design of better strategies to improve healthy human nutrition and to treat metabolic diseases. In this framework, nuclear receptors have emerged as key regulators of many cellular functions in response to lipid action. In this review, we will discuss the new concepts on the biology of the recently "adopted" nuclear receptors sensing oxy-sterols (LXR), bile acids (FXR) and fatty acids (PPARs) and their function in the integrated regulation of lipid and glucose metabolism. We will also address the role played by other orphan nuclear receptors, such as FTF, SHP and HNF-4, acting in concert with these lipid-sensing nuclear receptors in the regulation of cellular metabolism.