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: PMID:25263431   (View Abstract at PubMed)
DOI: DOI:10.1017/S0007114514002517   (Journal Full-text)

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.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CYP8B1Humancholesterol decreases expressionISOCyp8b1 (Rattus norvegicus)cholesterol decreases expression of Cyp8b1 mRNA in liverRGD 
Cyp8b1Ratcholesterol decreases expressionEXP cholesterol decreases expression of Cyp8b1 mRNA in liverRGD 
Cyp8b1Mousecholesterol decreases expressionISOCyp8b1 (Rattus norvegicus)cholesterol decreases expression of Cyp8b1 mRNA in liverRGD 
HMGCRHumancholesterol decreases expressionISOHmgcr (Rattus norvegicus)cholesterol decreases expression of Hmgcr mRNA in liverRGD 
HmgcrRatcholesterol decreases expressionEXP cholesterol decreases expression of Hmgcr mRNA in liverRGD 
HmgcrMousecholesterol decreases expressionISOHmgcr (Rattus norvegicus)cholesterol decreases expression of Hmgcr mRNA in liverRGD 
NR1H3Humancholesterol decreases expressionISONr1h3 (Rattus norvegicus)cholesterol decreases expression of LXR mRNA in liverRGD 
NR1H4Humancholesterol decreases expressionISONr1h4 (Rattus norvegicus)cholesterol decreases expression of Nr1h4 mRNA in liverRGD 
Nr1h3Ratcholesterol decreases expressionEXP cholesterol decreases expression of LXR mRNA in liverRGD 
Nr1h3Mousecholesterol decreases expressionISONr1h3 (Rattus norvegicus)cholesterol decreases expression of LXR mRNA in liverRGD 
Nr1h4Ratcholesterol decreases expressionEXP cholesterol decreases expression of Nr1h4 mRNA in liverRGD 
Nr1h4Mousecholesterol decreases expressionISONr1h4 (Rattus norvegicus)cholesterol decreases expression of Nr1h4 mRNA in liverRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Objects Annotated

Genes (Rattus norvegicus)
Abcg5  (ATP binding cassette subfamily G member 5)
Abcg8  (ATP binding cassette subfamily G member 8)
Cideb  (cell death-inducing DFFA-like effector b)
Cyp8b1  (cytochrome P450 family 8 subfamily B member 1)
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)
Cyp8b1  (cytochrome P450, family 8, subfamily b, polypeptide 1)
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)
CYP8B1  (cytochrome P450 family 8 subfamily B member 1)
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)

Objects referenced in this article
Gene ABCG5 ATP binding cassette subfamily G member 5 Homo sapiens
Gene ABCG8 ATP binding cassette subfamily G member 8 Homo sapiens
Gene ACAT2 acetyl-CoA acetyltransferase 2 Homo sapiens
Gene CIDEB cell death inducing DFFA like effector b Homo sapiens
Gene DGAT2 diacylglycerol O-acyltransferase 2 Homo sapiens
Gene Abcg5 ATP binding cassette subfamily G member 5 Mus musculus
Gene Abcg8 ATP binding cassette subfamily G member 8 Mus musculus
Gene Acat2 acetyl-Coenzyme A acetyltransferase 2 Mus musculus
Gene Cideb cell death-inducing DNA fragmentation factor, alpha subunit-like effector B Mus musculus
Gene Dgat2 diacylglycerol O-acyltransferase 2 Mus musculus
Gene Acat2 acetyl-CoA acetyltransferase 2 Rattus norvegicus
Gene Dgat2 diacylglycerol O-acyltransferase 2 Rattus norvegicus

Additional Information