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Phospholipid Transfer Protein–Deficient Mice Absorb Less Cholesterol
- Source :
- Arteriosclerosis, Thrombosis, and Vascular Biology. 27:2014-2021
- Publication Year :
- 2007
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2007.
-
Abstract
- Objective— Phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism and atherosclerosis. PLTP gene knockout (KO) mice show significant reduction of plasma cholesterol levels. Because small intestine is one of the major tissue expressing PLTP, we hypothesize that PLTP deficient small intestine absorbs less cholesterol, thus contributing to the diminishing of cholesterol levels in the plasma. Methods and Results— We used dual-labeled cholesterol/sitostanol feeding approach to study cholesterol absorption in PLTP KO and WT mice. We found that PLTP KO mice absorb significant less cholesterol than WT mice. Primary enterocytes isolated from PLTP KO enterocytes took up significant less cholesterol. Moreover, we observed that Niemann-Pick C1-like 1 (NPC1L1) mRNA levels were significantly decreased in the small intestine of PLTP KO mice. Next, we studied the secretion of cholesterol by enterocytes. The amounts of cholesterol transported to plasma and liver were significantly reduced in PLTP KO mice, compared with WT animals. Studies with isolated PLTP KO enterocytes revealed that the secretion of cholesterol via chylomicron and intestinal-HDL was significantly reduced. Furthermore, ATP-binding cassette transporters (ABC) A1 mRNA and microsomal triglyceride transfer protein (MTP) activity levels were significantly decreased in PLTP KO small intestine. Conclusion— These results indicate that PLTP deficiency results in reduced cholesterol uptake as well as secretion by the intestine. We suggest that PLTP could be a useful target to lower plasma cholesterol levels, thus reducing atherosclerosis.
- Subjects :
- medicine.medical_specialty
Ratón
Enterocyte
Biology
Mice
chemistry.chemical_compound
Internal medicine
Phospholipid transfer protein
Intestine, Small
medicine
Animals
Secretion
Phospholipid Transfer Proteins
Cells, Cultured
Gene knockout
Mice, Knockout
Cholesterol
Sitosterols
Small intestine
Enterocytes
medicine.anatomical_structure
Endocrinology
Intestinal Absorption
chemistry
lipids (amino acids, peptides, and proteins)
Cardiology and Cardiovascular Medicine
Lipoprotein
Subjects
Details
- ISSN :
- 15244636 and 10795642
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Accession number :
- edsair.doi.dedup.....9f1f3bafaad8506ef8188da69c3d3501