Nuclear receptors and transcription factors in the development of fatty liver disease.

Liver regulates certain key aspects of lipid metabolism including de novo lipogenesis, fatty acid oxidation, and lipoprotein uptake and secretion. Disturbances in these hepatic functions can contribute to the development of fatty liver disease. An understanding of the regulatory mechanisms influencing hepatic lipid homeostasis and systemic energy balance is therefore of paramount importance in gaining insights that might be useful in the management of fatty liver disease. In this regard, emerging evidence indicates that certain members of the nuclear receptor superfamily and some key transcription coactivators function as intracellular sensors to orchestrate hepatic lipid metabolism. Dysregulation of nuclear receptor-mediated transcriptional signaling and perturbations in the levels of their cognate endogenous ligands play a prominent role in the development of fatty liver disease. The potential of nuclear receptors, transcription coactivators as well as enzymes that participate in the synthesis and degradation of endogenous nuclear receptor ligands, as effective therapeutic targets for fatty liver disease needs evaluation.