Lipid Metabolism in Pregnancy. VI. Lipoprotein Composition and Hepatic Lipids in the Fed Pregnant Rat*

Abstract

To determine possible mechanisms for hyperlipidemia in the fed pregnant rat and to evaluate the rat as a model for hyperlipidemia in human pregnancy, we have measured lipoprotein composition and hepatic lipid content in age-matched nonpregnant and pregnant rats in mid and late gestation (days 12, 19, and 21). Up to the time of morning sacrifice, rats had ad libitum access to a standard chow diet containing 4.5% fat by weight. Four lipoprotein fractions were isolated by sequential ultracentrifugation: chylomicrons and very low, low, and high density lipoproteins (VLDL, LDL, and HDL, respectively). Preliminary feeding studies demonstrated the operationally defined chylomicron fraction to reflect fat absorption. Hepatic triglyceride and cholesterol were measured after Folch extraction and silicic acid treatment. In nonpregnant rats, 77–88% of the total triglyceride is contained in the chylomicron and VLDL fractions, with nearly equal amounts of triglyceride in each fraction. By late gestation (days 19 and 21), triglycerides increase 1.5 to 2.5-fold in chylomicrons and 2- to 3-fold in VLDL to the extent that significantly greater amounts of triglycerides are found in VLDL than in chylomicrons. These increases occur without significant alteration in percentage composition of chylomicron lipids or VLDL lipids and proteins. In LDL, no change is seen at days 12 and 19, but by day 21, LDL cholesterol and phospholipid increase in both absolute and relative amounts, resulting in a relative triglyceride reduction. Changes in HDL triglyceride and cholesterol at day 21 are small and not consistent in two experiments. In the liver, triglyceride concentrations on a wet weight basis decrease in late gestation while cholesterol concentrations are unchanged. The triglyceride increase in the fed pregnant rat is due to an accumulation of chylomicron and VLDL particles. The greatest increment occurs in VLDL lipids, pointing to endogenous triglyceride accumulation as the main basis for hyperlipidemia in rat pregnancy. Published data favor triglyceride overproduction rather than underremoval as the mechanism of VLDL triglyceride accumulation, and the reduced hepatic triglyceride content is consistent with a more efficient hepatic triglyceride release in late gestation. Despite the VLDL rise, percentage composition is unaltered in both rat and human pregnancy, indicating that the rat can serve as a useful model for VLDL metabolism in pregnancy.