Clearance of chylomicron triacylglycerol and cholesteryl ester from the plasma of streptozotocin-induced diabetic and hypercholesterolemic hypothyroid rats.

Labeled chylomicrons in thoracic duct lymph were collected after test meals containing 14C cholesterol and 2-3H glyceryl trioleate and were given by intravenous injection to groups of control rats, rats made diabetic by treatment with streptozotocin, and rats made hypothyroid and hypercholesterolemic by a diet containing cholesterol, peanut oil, cholic acid, and thiouracil. In the diabetic rats clearances from the plasma of chylomicron triacylglycerol and cholesteryl ester were impaired. A large variability in triacylglycerol clearance in diabetic rats was ascribed to variability in plasma triacylglycerol concentrations. Adipose tissue lipoprotein lipase activity was not impaired in the female diabetic rats used in this study. In the hypothyroid hypercholesterolemic rats chylomicron cholesteryl ester clearance from the plasma was impaired but chylomicron triacylglycerol was cleared efficiently, and adipose tissue lipoprotein lipase activity was similar to or greater than activity in controls. Ten minutes after intravenous injection most plasma radioactivity was recovered in lipoproteins of density less than 1.006 g/ml in all groups of rats, but relatively more was recovered at this density in both treatment groups. We suggest that chylomicron remnants accumulate in the plasma and contribute to the development of hyperlipemia in both treatment groups, but that the remnants formed in the diabetic rat are less depleted of triacylglycerol than the remnants formed in the hypothyroid hypercholesterolemic rat. It is suggested that factors other than measured lipoprotein lipase activities of adipose tissues may be important in determining the initial extent of hydrolysis of chylomicron triacyglycerol. We propose that the hypercholesterolemic hypothyroid rat is a useful model for the experimental production of the remnants of triacylglycerol-rich primary lipoproteins.