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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.
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.


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CRRD Object Information
CRRD ID: 15045610
Created: 2019-12-18
Species: All species
Last Modified: 2019-12-18
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.