Lack of the intestinal Muc1 mucin impairs cholesterol uptake and absorption but not fatty acid uptake in Muc1-/-mice

被引:22
作者
Wang, HH
Afdhal, NH
Gendler, SJ
Wang, DQH
机构
[1] Harvard Univ, Sch Med, Div Gastroenterol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr,Liver Ctr, Boston, MA 02215 USA
[3] Harvard Univ, Ctr Digest Dis, Boston, MA 02215 USA
[4] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Scottsdale, AZ 85259 USA
[5] Mayo Clin, Coll Med, Mol Biol & Tumor Biol Program, Scottsdale, AZ 85259 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2004年 / 287卷 / 03期
关键词
ATP-binding cassette (transporter); intestinal uptake; surface mucous coat; mucin gel; micelle; nutrition;
D O I
10.1152/ajpgi.00097.2004
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Before cholesterol and fatty acid molecules in the small intestinal lumen can interact with their possible transporters for uptake and absorption, they must pass through a diffusion barrier, which may modify the kinetics of nutrient assimilation. This barrier includes an unstirred water layer and a surface mucous coat, which is located at the intestinal lumen-membrane interface. In the present study, we investigated whether disruption of the mucin gene (Muc)1 may influence intestinal uptake and absorption of cholesterol and fatty acid in male Muc1(-/-) mice. The wild-type mice displayed relatively high levels of Muc1, Muc2, Muc3, and Muc4 mRNAs and relatively low levels of Muc5ac and Muc5b mRNAs in the small intestine. The absence of Muc1 mRNA and protein in the small intestines of Muc1(-/-) mice confirmed complete knockout of the Muc1 gene, but the mRNA expression for other mucin genes remained unchanged. Intestinal uptake and absorption of cholesterol but not palmitic acid were significantly reduced in Muc1(-/-) mice compared with the wild-type mice. However, knockout of the Muc1 gene did not impair either expression levels of the genes that encode intestinal sterol efflux transporters Abcg5 and Abcg8 and fatty acid transporter Fatp4 or small intestinal transit rates. We conclude that physiological levels of the epithelial mucin produced by the Muc1 gene are necessary for normal intestinal uptake and absorption of cholesterol in mice. Our study implies that because cholesterol absorption efficiency is reduced by similar to50% in Muc1-deficient mice, there may be one or more additional pathways for cholesterol absorption.
引用
收藏
页码:G547 / G554
页数:8
相关论文
共 56 条
[1]  
Abumrad N, 1998, J LIPID RES, V39, P2309
[2]   Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption [J].
Altmann, SW ;
Davis, HR ;
Zhu, LJ ;
Yao, XR ;
Hoos, LM ;
Tetzloff, G ;
Iyer, SPN ;
Maguire, M ;
Golovko, A ;
Zeng, M ;
Wang, LQ ;
Murgolo, N ;
Graziano, MP .
SCIENCE, 2004, 303 (5661) :1201-1204
[3]   Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters [J].
Berge, KE ;
Tian, H ;
Graf, GA ;
Yu, LQ ;
Grishin, NV ;
Schultz, J ;
Kwiterovich, P ;
Shan, B ;
Barnes, R ;
Hobbs, HH .
SCIENCE, 2000, 290 (5497) :1771-1775
[4]   Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. II. Duodenum and liver, gallbladder, and pancreas [J].
Buisine, MP ;
Devisme, L ;
Degand, P ;
Dieu, MC ;
Gosselin, B ;
Copin, MC ;
Aubert, JP ;
Porchet, N .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2000, 48 (12) :1667-1676
[5]   DIFFERENTIAL APOMUCIN EXPRESSION IN NORMAL AND NEOPLASTIC HUMAN GASTROINTESTINAL TISSUES [J].
CARRATO, C ;
BALAGUE, C ;
DEBOLOS, C ;
GONZALEZ, E ;
GAMBUS, G ;
PLANAS, J ;
PERINI, JM ;
ANDREU, D ;
REAL, FX .
GASTROENTEROLOGY, 1994, 107 (01) :160-172
[6]   LOCALIZATION OF MUCIN (MUC2 AND MUC3) MESSENGER-RNA AND PEPTIDE EXPRESSION IN HUMAN NORMAL INTESTINE AND COLON-CANCER [J].
CHANG, SK ;
DOHRMAN, AF ;
BASBAUM, CB ;
HO, SB ;
TSUDA, T ;
TORIBARA, NW ;
GUM, JR ;
KIM, YS .
GASTROENTEROLOGY, 1994, 107 (01) :28-36
[7]   INFLUENCE OF SMALL BOWEL TRANSIT-TIME ON DIETARY-CHOLESTEROL ABSORPTION IN HUMAN-BEINGS [J].
DELEON, MP ;
IORI, R ;
BARBOLINI, G ;
POMPEI, G ;
ZANIOL, P ;
CARULLI, N .
NEW ENGLAND JOURNAL OF MEDICINE, 1982, 307 (02) :102-103
[8]   A target for cholesterol absorption inhibitors in the enterocyte brush border membrane [J].
Detmers, PA ;
Patel, S ;
Hernandez, M ;
Montenegro, J ;
Lisnock, J ;
Pikounis, B ;
Steiner, M ;
Kim, D ;
Sparrow, C ;
Chao, YS ;
Wright, SD .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1486 (2-3) :243-252
[9]  
DIETSCHY JM, 1971, GASTROENTEROLOGY, V61, P932
[10]   Cholesterol absorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters Abcg5 and Abcg8 in mice [J].
Duan, LP ;
Wang, HH ;
Wang, DQH .
JOURNAL OF LIPID RESEARCH, 2004, 45 (07) :1312-1323