Intestinal nuclear receptors in HDL cholesterol metabolism

At the cellular level, de novo cholesterol synthesis and uptake of lipoprotein cholesterol are modulated through a negative feedback loop responding to elevations in intracellular cholesterol and regulated by a family of membranebound transcription factors named sterol-regulatory element binding proteins (SREBPs) ( 3 ). Earlier studies by Dietschy, Spady, and colleagues ( 4-6 ) provided evidence that, although virtually every tissue can synthesize sterol from acetyl-CoA, cholesterol may also be absorbed into the body from dietary sources, thus supporting an intestinal route of sterol infl ux. The elucidation of the molecular mechanisms underlying cholesterol absorption and the identifi cation of pharmacological compounds able to interfere with the absorptive process have greatly endorsed the intestinal apical and basolateral proteins as promising targets to modulate cholesterol metabolism ( 7, 8 ).