Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caco-2 Cells
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DNA-Binding Proteins / agonists
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DNA-Binding Proteins / metabolism*
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Down-Regulation / physiology
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Humans
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Intestinal Absorption / physiology
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Intestinal Mucosa / metabolism*
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Intestines / drug effects
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Liver X Receptors
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Membrane Glycoproteins
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Membrane Transport Proteins / metabolism*
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Mice
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Orphan Nuclear Receptors
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PPAR gamma / metabolism*
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Receptors, Cytoplasmic and Nuclear / agonists
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Saccharomyces cerevisiae Proteins
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Vesicular Transport Proteins
Substances
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DNA-Binding Proteins
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Liver X Receptors
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Membrane Glycoproteins
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Membrane Transport Proteins
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NCR1 protein, S cerevisiae
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NR1H3 protein, human
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Npc1l1 protein, mouse
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Nr1h3 protein, mouse
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Orphan Nuclear Receptors
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PPAR gamma
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Receptors, Cytoplasmic and Nuclear
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Saccharomyces cerevisiae Proteins
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Vesicular Transport Proteins