PMID- 24019513
OWN - NLM
STAT- MEDLINE
DCOM- 20131231
LR  - 20221109
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 42
DP  - 2013 Oct 18
TI  - Lipid absorption defects in intestine-specific microsomal triglyceride transfer 
      protein and ATP-binding cassette transporter A1-deficient mice.
PG  - 30432-30444
LID - S0021-9258(20)85715-9 [pii]
LID - 10.1074/jbc.M113.501247 [doi]
AB  - We have previously described apolipoprotein B (apoB)-dependent and -independent 
      cholesterol absorption pathways and the role of microsomal triglyceride transfer 
      protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways. 
      To assess the contribution of these pathways to cholesterol absorption and to 
      determine whether there are other pathways, we generated mice that lack MTP and 
      ABCA1, individually and in combination, in the intestine. Intestinal deletions of 
      Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%, 
      respectively, whereas their combined deletion reduced it by 59%. Acute 
      cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was 
      reduced by 92-95% when MTP was deleted in the intestine alone or together with 
      ABCA1. MTP deficiency significantly reduced triglyceride absorption, although 
      ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids, 
      but Mttp deficiency significantly increased intestinal levels of triglycerides 
      and free fatty acids. Accumulation of intestinal free fatty acids, but not 
      triglycerides, in Mttp-deficient intestines was prevented when mice were also 
      deficient in intestinal ABCA1. Combined deficiency of these genes increased 
      intestinal fatty acid oxidation as a consequence of increased expression of 
      peroxisome proliferator-activated receptor-gamma (PPARgamma) and carnitine 
      palmitoyltransferase 1alpha (CPT1alpha). These studies show that intestinal MTP and ABCA1 
      are critical for lipid absorption and are the main determinants of plasma and 
      intestinal lipid levels. Reducing their activities might lower plasma lipid 
      concentrations.
FAU - Iqbal, Jahangir
AU  - Iqbal J
AD  - From the Departments of Cell Biology and Pediatrics, State University of New York 
      Downstate Medical Center, Brooklyn, New York 11203 and.
FAU - Parks, John S
AU  - Parks JS
AD  - the Department of Pathology, Section on Lipid Sciences and Biochemistry, Wake 
      Forest School of Medicine, Winston-Salem, North Carolina 25157.
FAU - Hussain, M Mahmood
AU  - Hussain MM
AD  - From the Departments of Cell Biology and Pediatrics, State University of New York 
      Downstate Medical Center, Brooklyn, New York 11203 and. Electronic address: 
      Mahmood.Hussain@downstate.edu.
LA  - eng
GR  - R01 DK046900/DK/NIDDK NIH HHS/United States
GR  - DK-46900/DK/NIDDK NIH HHS/United States
GR  - HL049373/HL/NHLBI NIH HHS/United States
GR  - R01 HL119962/HL/NHLBI NIH HHS/United States
GR  - R29 DK046900/DK/NIDDK NIH HHS/United States
GR  - P01 HL049373/HL/NHLBI NIH HHS/United States
GR  - R56 DK046900/DK/NIDDK NIH HHS/United States
GR  - R01 DK081879/DK/NIDDK NIH HHS/United States
GR  - HL119962/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130909
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ABCA1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (Carrier Proteins)
RN  - 0 (Lipids)
RN  - 0 (PPAR gamma)
RN  - 0 (microsomal triglyceride transfer protein)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/genetics/*metabolism
MH  - Animals
MH  - Carnitine O-Palmitoyltransferase/genetics/metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Intestinal Absorption/*physiology
MH  - Intestinal Mucosa/*metabolism
MH  - Lipid Metabolism/*physiology
MH  - Lipids/*blood
MH  - Mice
MH  - Mice, Knockout
MH  - PPAR gamma/genetics/metabolism
PMC - PMC3798507
OTO - NOTNLM
OT  - ABCA1
OT  - Cholesterol
OT  - Intestine
OT  - Lipid Absorption
OT  - Lipid Metabolism
OT  - Lipids
OT  - Lipoprotein Secretion
OT  - Lipoprotein Structure
OT  - MTP
OT  - Triglyceride
EDAT- 2013/09/11 06:00
MHDA- 2014/01/01 06:00
PMCR- 2014/10/18
CRDT- 2013/09/11 06:00
PHST- 2013/09/11 06:00 [entrez]
PHST- 2013/09/11 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
PHST- 2014/10/18 00:00 [pmc-release]
AID - S0021-9258(20)85715-9 [pii]
AID - M113.501247 [pii]
AID - 10.1074/jbc.M113.501247 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Oct 18;288(42):30432-30444. doi: 10.1074/jbc.M113.501247. Epub 
      2013 Sep 9.