High-density lipoprotein cholesteryl ester and protein catabolism in hypercholesterolemic rats induced by copper deficiency.
High-density lipoprotein (HDL) catabolism induced by copper deficiency was examined in vivo in hypercholesterolemic Sprague-Dawley rats. Doubly labeled HDL was used to trace the catabolic pathways of both cholesteryl ester and protein moieties of HDL particles. The catabolic rate of removal from the plasma, as well as uptake by various tissues, was determined for each HDL component. Copper-deficient rats exhibited a 30% increase in HDL cholesterol concentration, confirming hypercholesterolemia. In addition, plasma volume was enlarged 38% in deficient animals, resulting in a significantly increased intravascular pool of all HDL components of at least 60%. These data emphasize the importance of determining plasma volume and total pool size of pertinent plasma components in this hypercholesterolemic model. The absolute catabolic rate (ACR) of HDL protein removal from the plasma was 369 +/- 22 and 278 +/- 12 micrograms/h in copper-deficient and control rats, respectively. The ACR of HDL cholesteryl ester was 647 +/- 37 micrograms/h in deficient animals and 321 +/- 13 micrograms/h in controls, suggesting that the mechanisms of selective clearance of HDL cholesteryl ester (compared with protein) were increased threefold by copper deficiency. Virtually all of the increased removal of HDL cholesteryl ester in deficient rats occurred in the liver. Since previous studies indicate that increased hepatic cholesterol excretion may not occur in copper deficiency, the present results suggest that cholesterol delivered to the liver as HDL cholesteryl ester is possibly reassembled into new HDL particles at an increased rate in copper-deficient rats.
Carr
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Department of Nutrition and Food Science, University of Arizona, Tucson 85721.
Lei
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D000818:Animals; D006332:Cardiomegaly; D002788:Cholesterol Esters / Q000097:blood* / Q000493:pharmacokinetics; D008076:Cholesterol, HDL / Q000097:blood*; D003300:Copper / Q000172:deficiency*; D006400:Hematocrit; D006937:Hypercholesterolemia / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013163:Splenomegaly; D014018:Tissue Distribution
D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D003300:Copper