THE EFFECTS OF CHOLESTEROL UPTAKE FROM HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS ON BILIARY STEROL SECRETION IN RATS WITH ESSENTIAL FATTY-ACID DEFICIENCY

High-density lipoprotein (HDL) participates in the transfer of cholest erol to the liver, in which it is subsequently excreted into bile as b ile acid and cholesterol. In this study, the effect of essential fatty -acid (EFA) deficiency on cholesterol contribution from HDL subfractio ns to bile was investigated. Rats that were rendered EFA-deficient ove r 4 weeks displayed changes in their plasma HDL subfractions and liver tissue fatty acids, Plasma linoleic (18:2n6), linolenic (18:3n3,) and arachidonic (20:4n6) acids decreased, whereas palmitoleic (16:1n7) an d eicosatrienoic (20:3n9) acids increased, EFA deficiency was confirme d by an elevation of the 20:3(n-9)/20:4(n-6) index. To examine the hep atic handling of lipoprotein-derived cholesterol, HDL2 and HDL3 from d onor rats were isolated, labeled with [C-14]-cholesterol, and injected iv into EFA-deficient and normal rats with a bile fistula, In HDL sub fractions from control rats, no significant variations were noted in t he specific activity of cholesterol output in both groups of EFA recip ient rats; however, the output of biliary bile acids was significantly decreased in EFA-deficient rats following the administration of label ed HDL3. In HDL2 and HDL3 originating from EFA-deficient rats, a decre ase in the specific activity of both biliary cholesterol and bile acid output was recorded in EFA-deficient rats. Concomitant with the defec tive HDL2- and HDL3-[C-14] cholesterol translocation into bile of EFA- deficient rats, increased hepatic very-low-density lipoprotein (VLDL)- [C-14] cholesterol secretion was observed in vivo, HDL2 and HDL3 parti cles, derived from EFA-deficient rats, had an altered composition incl uding a depletion in apo A-I and an enrichment in apo E isoforms, whic h are the the two major HDL apolipoproteins involved in the delivery o f cholesterol to the liver. Taken together, these results show that no rmal EFA status is necessary for efficient HDL-cholesterol processing by the liver.