RGD Reference Report - Impaired VLDL assembly: a novel mechanism contributing to hepatic lipid accumulation following ovariectomy and high-fat/high-cholesterol diets? - Rat Genome Database

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Impaired VLDL assembly: a novel mechanism contributing to hepatic lipid accumulation following ovariectomy and high-fat/high-cholesterol diets?

Authors: Côté, Isabelle  Chapados, Natalie A  Lavoie, Jean-Marc 
Citation: Côté I, etal., Br J Nutr. 2014 Nov 28;112(10):1592-600. doi: 10.1017/S0007114514002517. Epub 2014 Sep 29.
RGD ID: 15045610
Pubmed: (View Article at PubMed) PMID:25263431
DOI: Full-text: DOI:10.1017/S0007114514002517

The aim of the present study was to identify molecular mechanisms involved in liver fat and cholesterol accumulation in ovariectomised (Ovx) rats fed with high-cholesterol diets. VLDL assembly and bile acid metabolism were specifically targeted. After being either Ovx or sham-operated, the rats were fed a standard diet or a high-fat diet containing 0, 0·25 or 0·5 % cholesterol for 6 weeks. Although Ovx rats exposed to dietary cholesterol intake accumulated the greatest amount of hepatic fat and cholesterol, plasma cholesterol levels were lower (P< 0·05) in these animals than in the corresponding control rats. Accompanying this observation, ovariectomy and dietary cholesterol intake resulted in a down-regulation (P< 0·05) of the expression of genes associated with VLDL assembly, including microsomal TAG transfer protein, diacylglycerol acyltransferase 2, acyl-CoA:cholesterol acyltransferase 2 and apoB-100 as well as genes associated with bile acid metabolism including farnesoid X receptor and bile salt export pump (P< 0·01). These results indicate that high-fat/high-cholesterol diets and ovariectomy concomitantly disrupt hepatic lipid output through defects in VLDL assembly and, most probably, secretion. The results also point to a defect in hepatic bile acid secretion. The present study offers novel insights into intrahepatic lipid metabolism, which may be relevant to metabolic complications found in postmenopausal women.

Annotation

Disease Annotations    

Gene-Chemical Interaction Annotations    
cholesterol  (EXP,ISO)

Gene Ontology Annotations    

Biological Process

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Abcg5  (ATP binding cassette subfamily G member 5)
Abcg8  (ATP binding cassette subfamily G member 8)
Acat2  (acetyl-CoA acetyltransferase 2)
Cideb  (cell death-inducing DFFA-like effector b)
Cyp8b1  (cytochrome P450 family 8 subfamily B member 1)
Dgat2  (diacylglycerol O-acyltransferase 2)
Hmgcr  (3-hydroxy-3-methylglutaryl-CoA reductase)
Nr1h3  (nuclear receptor subfamily 1, group H, member 3)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Mus musculus)
Abcg5  (ATP binding cassette subfamily G member 5)
Abcg8  (ATP binding cassette subfamily G member 8)
Acat2  (acetyl-Coenzyme A acetyltransferase 2)
Cideb  (cell death-inducing DNA fragmentation factor, alpha subunit-like effector B)
Cyp8b1  (cytochrome P450, family 8, subfamily b, polypeptide 1)
Dgat2  (diacylglycerol O-acyltransferase 2)
Hmgcr  (3-hydroxy-3-methylglutaryl-Coenzyme A reductase)
Nr1h3  (nuclear receptor subfamily 1, group H, member 3)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Homo sapiens)
ABCG5  (ATP binding cassette subfamily G member 5)
ABCG8  (ATP binding cassette subfamily G member 8)
ACAT2  (acetyl-CoA acetyltransferase 2)
CIDEB  (cell death inducing DFFA like effector b)
CYP8B1  (cytochrome P450 family 8 subfamily B member 1)
DGAT2  (diacylglycerol O-acyltransferase 2)
HMGCR  (3-hydroxy-3-methylglutaryl-CoA reductase)
NR1H3  (nuclear receptor subfamily 1 group H member 3)
NR1H4  (nuclear receptor subfamily 1 group H member 4)


Additional Information