Transcriptional co-factors and hepatic energy metabolism.

ABSTRACT

After binding to their cognate DNA-binding partner, transcriptional co-factors exert their function through the recruitment of enzymatic, chromatin-modifying activities. In turn, the assembly of co-factor-associated multi-protein complexes efficiently impacts target gene expression. Recent advances have established transcriptional co-factor complexes as a critical regulatory level in energy homeostasis and aberrant co-factor activity has been linked to the pathogenesis of severe metabolic disorders including obesity, type 2 diabetes and other components of the Metabolic Syndrome. The liver represents the key peripheral organ for the maintenance of systemic energy homeostasis, and aberrations in hepatic glucose and lipid metabolism have been causally linked to the manifestation of disorders associated with the Metabolic Syndrome. Therefore, this review focuses on the role of distinct classes of transcriptional co-factors in hepatic glucose and lipid homeostasis, emphasizing pathway-specific functions of these co-factors under physiological and pathophysiological conditions.