Abstract
The SHR N -corpulent rat is a new genetically obese strain that is both hyperlipidemic and diabetic. The high density lipoprotein (HDL) fraction from 12-week-old obese males contained significantly greater amounts of protein (+83%), free (+72%) and esterified (+76%) cholesterol, phospholipid (+94%), and triglyceride (+78%). HDL from obese rats were also enriched in C apolipoproteins (apo C-III 0 and apo C-III 3) but had similar relative amounts of both apo A-I and apo E compared to HDL from their lean littermates. HDL protein turnover, measured with 125I-labeled HDL, showed that obese rats had a smaller fractional catabolic rate (FCR) than lean rats, but due to their much larger HDL pool size, they had a significantly higher rate of HDL protein catabolism (obese, 1.98 ± 0.07 mg/whole animal/h v lean, 1.32 ± 0.05 mg/whole animal/h). Therefore, under steady-state conditions, HDL protein production must also have been increased in the obese animals. To determine whether the increased catabolism of HDL protein was associated with increased catabolism of cholesteryl ester (CE), tissue uptake of HDL CE was measured using the nonhydrolyzable ether analogue [ 3H]cholesteryl linoleyl ether. After four hours 41.6 ± 1.6% of the injected dose was cleared from the plasma of lean rats compared with 37.0 ± 1.1% from the plasma of obese rats. In both groups almost one third of the injected dose appeared in the liver ( (lean, 31.01 ± 1.95% v obese, 30.07 ± 1.17%). However, taking into account that the HDL CE pool in the obese rats was more than 80% larger than in the lean rats, total hepatic catabolism of HDL CE was much greater in the obese animals. Adipose tissue and the small intestine also catabolized more HDL CE in the obese v lean rats. We conclude that the increased levels of HDL protein and HDL CE in the obese rats are due predominantly to overproduction rather than to impaired catabolism of HDL, and that the liver remains quantitatively the most important site for HDL CE catabolism in these animals.
Published Version
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