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Hepatic Cholesterol and Fatty Acid Synthesis in Pregnant and Fetal Rats: Effect of Maternal Dietary Fat and Cholestyramine^{1, 2,}

Departments of Pathology ^* Paediatrics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4

Previous studies from this laboratory have demonstrated that 20% rather than 5% (wt/wt) safflower oil or addition of 5% (wt/wt) cholestyramine to the diet of pregnant rats leads to an increase in the activity of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, in the fetal liver. Total cholesterol, however, was not altered in fetal plasma or liver. The effect of these diets on cholesterol and fatty acid synthesis in vivo was therefore studied in fetal and maternal liver. In fetuses of rats fed a reference nonpurified diet, rates of hepatic cholesterol and fatty acid synthesis decreased from gestation d 20 to 21. In contrast, total and active 3-hydroxy-3-methylglutaryl CoA reductase activity increased. Adding cholestyramine to the diet or modifying the quantity of safflower oil fed had no effect on fetal hepatic lipogenesis. Maternal hepatic cholesterol synthesis was greater in rats fed cholestyramine, whereas fatty acid synthesis was lower in the dams fed the diet containing 20% compared with 5% safflower oil. The results suggest near-term fetal liver 3-hydroxy-3-methylglutaryl CoA reductase activities do not reflect fetal cholesterol synthesis in vivo.

KEY WORDS: • cholesterol synthesis • rats • liver development • 3-hydroxy-3-methylglutaryl CoA reductase

¹ Supported by a grant from the Medical Research Council of Canada.

² Presented in part at the 81st Annual Meeting of The American Oil Chemists' Society, April 1990, Baltimore, MD [Haave, N. C. & Innis, S. M. (1990) Effect of maternal diet fat on fatty acids and cholesterol synthesis in fetal rat liver. INFORM 1:280 (abs. C6)].

³ To whom correspondence should be addressed.

Manuscript received 24 September 1990. Revision accepted 25 March 1991.