Accelerated lipid absorption in mice overexpressing intestinal SR-BI.
Dietary cholesterol absorption contributes to a large part of the circulating cholesterol. However, the mechanism of sterol intestinal uptake is not clearly elucidated. Scavenger receptor class B type I (SR-BI), major component in the control of cholesterol homeostasis, is expressed in the intestine, but its role in this organ remains unclear. We have generated transgenic mice overexpressing SR-BI primarily in the intestine by using the mouse SR-BI gene under the control of intestinal specific "apoC-III enhancer coupled with apoA-IV promoter." We found SR-BI overexpression with respect to the natural protein along the intestine and at the top of the villosities. After a meal containing [(14)C]cholesterol and [(3)H]triolein, SR-BI transgenic mice presented a rise in intestinal absorption of both lipids that was not due to a defect in chylomicron clearance nor to a change in the bile flow or the bile acid content. Nevertheless, SR-BI transgenic mice showed a decrease of total cholesterol but an increase of triglyceride content in plasma without any change in the high density lipoprotein apoA-I level. Thus, we described for the first time a functional role in vivo for SR-BI in cholesterol but also in triglyceride intestinal absorption.
Bietrix
Florence
F
INSERM U 563, Centre de Physiopathologie de Toulouse Purpan, Département Lipoprotéines et Médiateurs Lipidiques, IFR30 and Université Paul Sabatier, 31024 Toulouse Cedex 3, France.
Yan
Daoguang
D
Nauze
Michel
M
Rolland
Corinne
C
Bertrand-Michel
Justine
J
Coméra
Christine
C
Schaak
Stephane
S
Barbaras
Ronald
R
Groen
Albert K
AK
Perret
Bertrand
B
Tercé
François
F
Collet
Xavier
X
D000042:Absorption; D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry; D001647:Bile Acids and Salts / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D002914:Chylomicrons / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D006706:Homeostasis; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051116:Receptors, Scavenger / Q000737:chemistry; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D014018:Tissue Distribution; D014280:Triglycerides / Q000378:metabolism; D014304:Triolein / Q000737:chemistry
D001053:Apolipoproteins; D001647:Bile Acids and Salts; D002914:Chylomicrons; D018076:DNA, Complementary; D008055:Lipids; D008074:Lipoproteins; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; D014304:Triolein; D002784:Cholesterol