Niemann–Pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine

• DOI: 10.1016/j.bbrc.2005.12.137
• Publication Date: 2006-01-06T07:11:08Z
• Authors: Caroline Duval; Véronique Touche; Anne Tailleux; Jean-Charles Fruc...; Catherine Fievet; Véronique Clavey; Bart Staels; Sophie Lestavel
• Keywords: 0303 health sciences; Membrane Glycoproteins; Saccharomyces cerevisiae Proteins; Vesicular Transport Proteins; Down-Regulation; Membrane Transport Proteins; Receptors, Cytoplasmic and Nuclear; Orphan Nuclear Receptors; DNA-Binding Proteins; Intestines; PPAR gamma; Mice; 03 medical and health sciences; Intestinal Absorption; Animals; Humans; Caco-2 Cells; Intestinal Mucosa; Liver X Receptors

Niemann-Pick C1 like 1 (NPC1L1) is a protein critical for intestinal cholesterol absorption. The nuclear receptors peroxisome proliferator-activated receptor alpha (PPARalpha) and liver X receptors (LXRalpha and LXRbeta) are major regulators of cholesterol homeostasis and their activation results in a reduced absorption of intestinal cholesterol. The goal of this study was to define the role of PPARalpha and LXR nuclear receptors in the regulation of NPC1L1 gene expression. We show that LXR activators down-regulate NPC1L1 mRNA levels in the human enterocyte cell line Caco-2/TC7, whereas PPARalpha ligands have no effect. Furthermore, NPC1L1 mRNA levels are decreased in vivo, in duodenum of mice treated with the LXR agonist T0901317. In conclusion, the present study identifies NPC1L1 as a novel LXR target gene further supporting a crucial role of LXR in intestinal cholesterol homeostasis.