RGD Reference Report - Abnormal hepatobiliary and circulating lipid metabolism in the Long-Evans Cinnamon rat model of Wilson's disease. - Rat Genome Database

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Abnormal hepatobiliary and circulating lipid metabolism in the Long-Evans Cinnamon rat model of Wilson's disease.

Authors: Levy, E  Brunet, S  Alvarez, F  Seidman, E  Bouchard, G  Escobar, E  Martin, S 
Citation: Levy E, etal., Life Sci. 2007 Mar 27;80(16):1472-83. Epub 2007 Jan 20.
RGD ID: 2292672
Pubmed: PMID:17303181   (View Abstract at PubMed)
DOI: DOI:10.1016/j.lfs.2007.01.017   (Journal Full-text)

Long-Evans Cinnamon (LEC) rats exhibit a genetic defect in Atp7b gene, which is homologous to the human Wilson's disease gene, resulting in an inability to mobilize copper from the liver. This study was undertaken to gain insight into the relationship between liver copper accumulation and plasma lipid profile, circulating lipoprotein composition, hepatic sterol metabolism and biliary lipid secretion rates in 12-week-old LEC rats compared to control Long-Evans rats. Concomitant with hepatic copper deposition, LEC rats displayed increased content of triglycerides (TGs), free cholesterol (FC) and cholesteryl ester (CE) in the liver. Hepatic concentrations of malondialdehyde (MDA), an index of lipid peroxidation were also significantly elevated in LEC rats (50%). This steatosis was associated with aberrant microsomal apolipoprotein (apo) B-100 and microsomal triglyceride transfer protein (MTP) content, hypotriglyceridemia, hypocholesterolemia and abnormalities in both circulating lipoprotein composition and size. Atypical hepatobiliary sterol metabolism was established by the assessment of the activity of key intracellular enzymes for cholesterol homeostasis, which demonstrated, with respect to controls, a 40% reduction in 3-hydroxy-3-methylglutaryl coenzyme A reductase, a 30% reduction in cholesterol 7alpha-hydroxylase, and a 54% reduction in acyl CoA:cholesterol acyltransferase. During a 6-h biliary drainage, a decline in the bile acid output was recorded and might be linked to the low protein expression of the bile salt export pump (BSEP or ABCB11). Our data emphasize the crucial role of copper balance in hepatic sterol homeostasis and lipoprotein metabolism in LEC rats. Additional studies are needed to delineate the mechanisms of these disorders.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Wilson disease  ISOAtp7b (Rattus norvegicus)2292672; 2292672DNA:deletion:exonRGD 
Wilson disease  IAGP 2292672DNA:deletion:exonRGD 
Wilson disease  IAGP 2292672 RGD 
Wilson disease  ISOHmgcr (Rattus norvegicus)2292672; 2292672 RGD 
Wilson disease  IDA 2292672 RGD 

Phenotype Annotations    Click to see Annotation Detail View
Objects Annotated

Genes (Rattus norvegicus)
Atp7b  (ATPase copper transporting beta)
Atp7bhts  (ATPase copper transporting beta; hepatitis)
Hmgcr  (3-hydroxy-3-methylglutaryl-CoA reductase)

Genes (Mus musculus)
Atp7b  (ATPase, Cu++ transporting, beta polypeptide)
Hmgcr  (3-hydroxy-3-methylglutaryl-Coenzyme A reductase)

Genes (Homo sapiens)
ATP7B  (ATPase copper transporting beta)
HMGCR  (3-hydroxy-3-methylglutaryl-CoA reductase)


Additional Information