Effect of cholesterol, cholic acid and cholestyramine administration on the intestinal mRNA expressions related to cholesterol and bile acid metabolism in the rat.
OBJECTIVE
To evaluate the importance of cholesterol and bile acid concentrations in the intestinal lumen to cholesterol homeostasis, we investigated the effect of cholesterol-, bile salt- or cholestyramine-administration on the regulation of intestinal mRNA related to cholesterol and bile acid metabolism.


METHODS
Male Wistar rats fed on standard laboratory chow (AIN-93) were allocated into four experimental groups: (i) control group; (ii) cholesterol group (CH), which was fed cholesterol in diet (2% [w/w]) for 14 days; (iii) cholic acid (CA) group, which was fed CA in diet (1% [w/w]) for 14 days; (iv) cholestyramine (CT) group, which was fed CT in diet (5% [w/w]) for 14 days. Blood, liver and small intestine were obtained after 14 days. Serum lipids and bile acids were measured by colorimetric assays, and hepatic and intestinal mRNA relating to lipid and bile acid metabolism was studied by reverse transcription-polymerase chain reaction.


RESULTS
Intestinal ABCG8, liver X receptor alpha, small heterodimer partner (SHP) and sterol regulatory element binding protein 1c (SREBP-1c) mRNA expressions were markedly increased in the CH group. Intestinal multidrug resistance associated protein (MRP) 2 and MRP3 mRNA expressions were markedly increased in the CA group. In the CT group intestinal MRP2, ABCG5, ABCG8, SHP and SREBP-1c mRNA expressions were markedly decreased.


CONCLUSIONS
The bile acid availability in the intestinal lumen alters the expression of various intestinal mRNA relating to not only bile acid metabolism, but also lipid metabolism. Though the mechanism of the intestinal SHP elevation is unclear, cholesterol feeding may affect the intestinal bile acid metabolism via intestinal SHP expression.
Kamisako
Toshinori
T
Department of Hygiene, Kinki University School of Medicine, Osakasayama, Japan. kamisako@med.kindai.ac.jp
Ogawa
Hiroshi
H
Yamamoto
Kazuo
K
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology*; D019826:Cholic Acid / Q000097:blood / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D002784:Cholesterol; D002792:Cholestyramine Resin; D019826:Cholic Acid; D004268:DNA-Binding Proteins; D008074:Lipoproteins; D000071518:Liver X Receptors; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1; C423013:Abcc2 protein, rat; C480692:Abcg5 protein, rat; C480693:Abcg8 protein, rat; C000605215:Nr1h3 protein, rat; C099713:nuclear receptor subfamily 0, group B, member 2; C114462:multidrug resistance-associated protein 3