| ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums. | |
| | |
MedLine Citation:
|
PMID: 20488799 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
High-responding opossums are susceptible to developing hypercholesterolemia on a high-cholesterol diet, but low-responding opossums are resistant. The observation of low biliary cholesterol and low biliary phospholipids in high responders suggested that the ABCB4 gene affects response to dietary cholesterol. Two missense mutations (Arg29Gly and Ile235Leu) were found in the ABCB4 gene of high responders. High responders (ATHH strain) were bred with low responders (ATHE or ATHL strain) to produce F1 and F2 progeny in two different genetic crosses (KUSH6 and JCX) to determine the effect of ABCB4 allelic variants on plasma cholesterol concentrations after a dietary challenge. Pedigree-based genetic association analyses consistently implicated a variant in ABCB4 or a closely linked locus as a major, but not the sole, genetic contributor to variation in the plasma cholesterol response to dietary cholesterol. High responders, but not low responders, developed liver injury as indicated by elevated plasma biomarkers of liver function, probably reflecting damage to the canalicular membrane by bile salts because of impaired phospholipid secretion. Our results implicate ABCB4 as a major determinant of diet-induced hypercholesterolemia in high-responding opossums and suggest that other genes interact with ABCB4 to regulate lipemic response to dietary cholesterol. |
| | |
Authors:
|
Jeannie Chan; Michael C Mahaney; Rampratap S Kushwaha; Jane F VandeBerg; John L VandeBerg |
Related Documents
:
|
16894239 - Ezetimibe inhibits the incorporation of dietary oxidized cholesterol into lipoproteins. 3625039 - Contraceptive steroids increase cholesterol in bile: mechanisms of action. 1542009 - Excessive cholesterolemic response in analbuminemic rats fed a cholesterol-rich diet co... 3668389 - Regulation of rat hepatic cholesterol metabolism. effects of lipoprotein composition on... 17201649 - Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma cholestero... 8109889 - Comparison of dietary casein and soybean protein effects on plasma lipid and gastrin le... 495549 - Effect of fiber from fruits and vegetables on metabolic responses of human subjects. ii... 10879449 - Training and natural immunity: effects of diets rich in fat or carbohydrate. 7651379 - Effect of long term feeding of rice bran oil upon lipids and lipoproteins in rats. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-05-20 |
Journal Detail:
|
Title: Journal of lipid research Volume: 51 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2010 Oct |
Date Detail:
|
Created Date: 2010-09-10 Completed Date: 2011-01-24 Revised Date: 2012-05-07 |
Medline Journal Info:
|
Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
|
Languages: eng Pagination: 2922-8 Citation Subset: IM |
Affiliation:
|
Southwest National Primate Research Center, Southwest Foundation for Biomedical Research , San Antonio, TX, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cholesterol / blood DNA, Complementary / metabolism Dietary Fats / pharmacology Genotype Hypercholesterolemia / etiology, genetics*, metabolism Membrane Transport Proteins / genetics*, metabolism Opossums P-Glycoproteins / genetics, metabolism Triglycerides / blood |
| Grant Support | |
ID/Acronym/Agency:
|
R01 DK-065058/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/DNA, Complementary; 0/Dietary Fats; 0/Membrane Transport Proteins; 0/P-Glycoproteins; 0/Triglycerides; 0/multidrug resistance protein 3; 57-88-5/Cholesterol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Elevated hepatic fatty acid elongase-5 activity corrects dietary fat-induced hyperglycemia in obese ...
Next Document: Deficiency in hepatic ATP-citrate lyase affects VLDL-triglyceride mobilization and liver fatty acid ...