Document Detail


Hepatic overexpression of Abcb11 in mice promotes the conservation of bile acids within the enterohepatic circulation.
MedLine Citation:
PMID:  23139217     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The bile salt export pump, encoded by ABCB11, is the predominant canalicular transport protein for biliary bile acid secretion. The level of ABCB11 expression in humans is widely variable yet the impact of this variability on human disease is not well defined. We aim to determine the effect of hepatic Abcb11 overexpression on the enterohepatic circulation (EHC) in mice. We used a stable isotope dilution technique in transgenic mice overexpressing hepatic Abcb11 (TTR-Abcb11) to determine the pool size, fractional turnover rate (FTR), and synthesis rate of the primary bile acid, cholic acid (CA). The gallbladder was cannulated to determine bile flow, bile acid composition, and the biliary secretion rates of CA, total bile acids, phospholipid, and cholesterol. The combined data allowed for estimation of the CA cycling time and the fraction of CA lost per cycle. Hepatic and intestinal gene and protein expression were determined by qPCR and Western blot. Abcb11 overexpression strongly decreased FTR and synthesis rate of CA. Abcb11 overexpression decreased the fraction of CA that was lost per cycle of the EHC. Hepatic expression of Cyp7a1 was suppressed by nearly 50% and ileal expression of FGF15 was increased more than eightfold in TTR-Abcb11 mice. Despite the increased intestinal reabsorption of bile acids, ileal Asbt expression was suppressed. Hepatic Abcb11 overexpression in mice increases the conservation of bile acids within the enterohepatic circulation. These data provide strong evidence for the existence of feed-forward communication between hepatic expression of a bile acid transport protein and the intestine.
Authors:
Anne S Henkel; Karin E R Gooijert; Rick Havinga; Renze Boverhof; Richard M Green; Henkjan J Verkade
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-08
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  304     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-03-05     Revised Date:  2014-06-09    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G221-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Animals
Bile / metabolism*
Bile Acids and Salts / metabolism*
Blotting, Western
Cholesterol / metabolism
Cholesterol 7-alpha-Hydroxylase / metabolism
Cholic Acid / metabolism
Enterohepatic Circulation*
Feedback, Physiological
Fibroblast Growth Factors / metabolism
Gene Expression Regulation
Ileum / metabolism
Indicator Dilution Techniques
Liver / metabolism*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Organic Anion Transporters, Sodium-Dependent / metabolism
Phospholipids / metabolism
Prealbumin / genetics
Promoter Regions, Genetic
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Symporters / metabolism
Up-Regulation
Grant Support
ID/Acronym/Agency:
F32DK076342/DK/NIDDK NIH HHS; R01 DK093807/DK/NIDDK NIH HHS; R01DK080810/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Abcb11 protein, mouse; 0/Bile Acids and Salts; 0/Organic Anion Transporters, Sodium-Dependent; 0/Phospholipids; 0/Prealbumin; 0/Symporters; 0/fibroblast growth factor 15, mouse; 145420-23-1/sodium-bile acid cotransporter; 62031-54-3/Fibroblast Growth Factors; 97C5T2UQ7J/Cholesterol; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase; EC 1.14.13.17/Cyp7a1 protein, mouse; G1JO7801AE/Cholic Acid
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