Studies on the etiology of the hyperlipemia in rats fed an atherogenic diet

The etiology of the hyperlipemia which occurs in cholesterol- and fat-fed hypothyroid rats was investigated. In hyperlipemic rats the disappearance rate of 125I-labeled chylomicron remnants was markedly prolonged (t1/2 of 13.1 +/- 0.9 min versus t1/2 of 2.1 +/- 0.5 min in controls). However the ability of isolated livers from these rats to remove remnants was not significantly different from that of control livers. This suggested that the delay in removal was due to an increase in the circulating remnant concentration without a removal defect. 125I-labeled VLDL from hyperlipemic rats was removed by isolated livers from normal rats at a rate similar to normal chylomicrons or hepatic VLDL and more slowly than normal remnants. This suggested that remnants were not the principal constituents of the VLDL in these animals. Moreover when these VLDL were injected into intact normal rats they were removed with a t1/2 (5.5 +/- 1.2 min) comparable to normal VLDL rather than remnants. Finally, livers from hyperlipemic rats were perfused and the composition of the VLDL secreted was examined Compared to controls or animals fed propylthiouracil, these livers secreted a particle which was triglyceride-poor and cholesteryl ester-rich. Thus, the etiology of the hyperlipemia has several components. There is both expansion of the remnant pool and secretion of an abnormal lipoprotein.