Document Detail


Genetic factors at the enterocyte level account for variations in intestinal cholesterol absorption efficiency among inbred strains of mice.
MedLine Citation:
PMID:  11714851     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interindividual and interstrain variations in cholesterol absorption efficiency occur in humans and animals. We investigated physiological biliary and small intestinal factors that might determine variations in cholesterol absorption efficiency among inbred mouse strains. We found that there were significant differences in cholesterol absorption efficiency measured by plasma, fecal, and lymphatic methods: <25% in AKR/J, C3H/J, and A/J strains; 25-30% in SJL/J, DBA/2J, BALB/cJ, SWR/J, and SM/J strains; and 31-40% in C57L/J, C57BL/6J, FVB/J, and 129/SvJ strains. In (AKRxC57L)F1 mice, the cholesterol absorption efficiency (31 +/- 6%) mimicked that of the C57L parent (37 +/- 5%) and was significantly higher than in AKR mice (24 +/- 4%). Although biliary bile salt compositions and small intestinal transit times were similar, C57L mice displayed significantly greater bile salt secretion rates and pool sizes than AKR mice. In examining lymphatic cholesterol transport in the setting of a chronic biliary fistula, C57L mice displayed significantly higher cholesterol absorption rates compared with AKR mice. Because biliary and intestinal transit factors were accounted for, we conclude that genetic variations at the enterocyte level determine differences in murine cholesterol absorption efficiency, with high cholesterol absorption likely to be a dominant trait. This study provides baseline information for identifying candidate genes that regulate intestinal cholesterol absorption at the cellular level.
Authors:
D Q Wang; B Paigen; M C Carey
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of lipid research     Volume:  42     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-20     Completed Date:  2002-01-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1820-30     Citation Subset:  IM    
Affiliation:
Department of Medicine, Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School and Harvard Digestive Diseases Center, Boston, MA 02115, USA. dqwang@caregroup.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile / chemistry
Bile Acids and Salts / analysis
Biliary Fistula
Cholesterol / blood
Cholesterol, Dietary / pharmacokinetics*
Crosses, Genetic
Enterocytes / metabolism*
Female
Gallbladder / metabolism
Gastrointestinal Transit
Intestinal Absorption / genetics*
Lymphatic System / metabolism
Male
Mice
Mice, Inbred A
Mice, Inbred AKR
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Inbred Strains
Phospholipids / metabolism
Grant Support
ID/Acronym/Agency:
DK 34854/DK/NIDDK NIH HHS; DK 36588/DK/NIDDK NIH HHS; DK 52911/DK/NIDDK NIH HHS; DK 54012/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholesterol, Dietary; 0/Phospholipids; 57-88-5/Cholesterol

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