Phospholipid transfer protein-deficient mice absorb less cholesterol.
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.


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.


CONCLUSIONS
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.
Liu
Ruijie
R
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, 450 Clarkson Ave, Box 5, Brooklyn, NY 11203, USA.
Iqbal
Jahangir
J
Yeang
Calvin
C
Wang
David Q-H
DQ
Hussain
M Mahmood
MM
Jiang
Xian-Cheng
XC
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D007408:Intestinal Absorption / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000502:physiology*; D012855:Sitosterols / Q000378:metabolism
D049294:Phospholipid Transfer Proteins; D012855:Sitosterols; D002784:Cholesterol; C021255:stigmastanol