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

• Published in: British journal of nutrition Vol. 112; no. 10; pp. 1592 - 1600
• Main Authors: Côté, Isabelle, Chapados, Natalie A., Lavoie, Jean-Marc
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 28.11.2014
• Subjects: Animals; Apolipoprotein B-100 - metabolism; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters - metabolism; Bile Acids and Salts - metabolism; Biological and medical sciences; Carrier Proteins - metabolism; Cholesterol; Cholesterol, Dietary - adverse effects; Cholesterol, Dietary - metabolism; Diet; Diet, High-Fat - adverse effects; Dietary Fats - adverse effects; Dietary Fats - metabolism; Down-Regulation; Estrogens - deficiency; Fatty Liver - etiology; Fatty Liver - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Lipid Metabolism; Lipids; Lipoproteins, VLDL - biosynthesis; Lipoproteins, VLDL - metabolism; Liver; Liver - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Menopause; Metabolism; Metabolism and Metabolic Studies; Oils & fats; Other diseases. Semiology; Ovariectomy; Rats, Sprague-Dawley; Receptors, Cytoplasmic and Nuclear - metabolism; Rodents; Sterol O-Acyltransferase - metabolism; Sterol O-Acyltransferase 2; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Microsomal TAG transfer protein; Hepatic cholesterol accumulation; Hepatic steatosis; VLDL; Dietary cholesterol; Nutrition; Ovariectomy; Digestive system; Liver; Hepatic disease; Lipids; Cholesterol; Protein; Feeding; Fatty liver; Diet; Fat; Transfer; Digestive diseases
• ISSN: 0007-1145; 1475-2662
• 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.