Phospholipid transfer protein-deficient mice absorb less cholesterol

Ruijie Liu, Jahangir Iqbal, Calvin Yeang, David Q.H. Wang, M. Mahmood Hussain, Xian Cheng Jiang

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2014-2021
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume27
Issue number9
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Fingerprint

Phospholipid Transfer Proteins
Cholesterol
Knockout Mice
Enterocytes
Small Intestine
mouse phospholipid transfer protein
Atherosclerosis
Chylomicrons
Protein Deficiency
Messenger RNA
Gene Knockout Techniques
ATP-Binding Cassette Transporters

Keywords

  • Cholesterol absorption
  • Enterocytes
  • Intestine
  • Lipoproteins
  • PLTP gene knockout

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Phospholipid transfer protein-deficient mice absorb less cholesterol. / Liu, Ruijie; Iqbal, Jahangir; Yeang, Calvin; Wang, David Q.H.; Hussain, M. Mahmood; Jiang, Xian Cheng.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 27, No. 9, 01.09.2007, p. 2014-2021.

Research output: Contribution to journalArticle

Liu, Ruijie ; Iqbal, Jahangir ; Yeang, Calvin ; Wang, David Q.H. ; Hussain, M. Mahmood ; Jiang, Xian Cheng. / Phospholipid transfer protein-deficient mice absorb less cholesterol. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2007 ; Vol. 27, No. 9. pp. 2014-2021.
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AB - 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.

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