Intestinal nuclear receptors in HDL cholesterol metabolism.

The intestine plays a pivotal role in cholesterol homeostasis by functioning as an absorptive and secretory organ in the reverse cholesterol transport pathway. Enterocytes control cholesterol absorption, apoAI synthesis, HDL biogenesis, and nonbiliary cholesterol fecal disposal. Thus, intestine-based therapeutic interventions may hold promise in the management of diseases driven by cholesterol overload. Lipid-sensing nuclear receptors (NRs) are highly expressed in the intestinal epithelium and regulate transcriptionally the handling of cholesterol by the enterocytes. Here, we discuss the NR regulation of cholesterol fluxes across the enterocytes with special emphasis on NR exploitation as a bona fide novel HDL-raising strategy.