Secretion of Cholesterol-Rich Lipoproteins by Perfused Livers of Hypercholesterolemic Rats

Ratsmaintained on a high-fat diet supplemented withpropylthiouracil develop ahyper- cholesterolemia, anincreased serumlevel ofapolipo- protein (apo) E,abnormal verylowdensity lipoproteins (VLDL)andlowdensity lipoproteins (LDL), anda fatty liver whichcontains cholesterol esterasits majorlipid. Thefatty liver secretes apoEintoare- circulating perfusate atasignificantly higher rateand produces cholesterol ester-rich, apoC-deficient VLDL withslower electrophoretic mobility thanthetriacyl- glycerol-rich VLDL produced byperfused normal livers. LDL,secreted insignificant quantities bythe perfused fatty liver, butnotbythenormal liver, is also cholesterol rich andcontains apoEaswell asapoB. Theincorporation of(3H)leucine intoapoVLDLand apoLDLsecreted bythelivers ofthehypercholes- terolemic animals andtheapoVLDLsecreted bythe normal liver corresponds tothepattern visualized when theapoproteins areseparated bypolyacrylamide gel electrophoresis. Similar patterns arenoted whennon- recirculating perfusates arestudied. Theseresults indicate that thecholesterol ester-rich, apoC-deficient VLDL andtheapoE-containing LDL foundinthe serumofhypercholesterolemic ratsarenotsolely catabolic remnants ofVLDL andchylomicrons but aresecreted bytheliver. Separation oftheperfusate lipoproteins byagarose gelfiltration revealed that Aportion ofthis workwaspresented totheAmerican Heart Association, November 1978, Dallas, Tex., andappeared in abstract formin1978. Circulation. 58:II-77. Dr.WongisaFellow oftheCanadian HeartFoundation. Dr.Dolphin isaScholar oftheCanadian HeartFoundation. Dr.Noel's present address isD6partement deBiochimie, Universit6 deMontr6al, Montr6al, Quebec, Canada; Dr. Wong'spresent address isThe Rockefeller University, NewYork; Dr.Rubinstein andDr.Dolphin's present address isDepartment ofBiochemistry, Dalhousie University, Hali- fax, NovaScotia, Canada; andDr.Dory's present address is