Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats

S. P. Noel, L. Wong, P. J. Dolphin, Ladislav Dory, D. Rubenstein

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51 Citations (Scopus)

Abstract

Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VDLD) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [3H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apo VLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are sepaeated by polyacrylamide gel electrophoresis. Similar patterns are noted when nonrecirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.

Original languageEnglish
Pages (from-to)674-683
Number of pages10
JournalUnknown Journal
Volume64
Issue number2
DOIs
StatePublished - 1 Jan 1979

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Apolipoproteins E
Liver
LDL Lipoproteins
Cholesterol Esters
Fatty Liver
Apolipoproteins C
Apoproteins
Lipoproteins
Chylomicron Remnants
Cholesterol
Propylthiouracil
VLDL Lipoproteins
Apolipoproteins
Apolipoproteins B
High Fat Diet
HDL Lipoproteins
lipoprotein cholesterol
Hypercholesterolemia
Serum
Leucine

Cite this

Noel, S. P. ; Wong, L. ; Dolphin, P. J. ; Dory, Ladislav ; Rubenstein, D. / Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats. In: Unknown Journal. 1979 ; Vol. 64, No. 2. pp. 674-683.
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title = "Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats",
abstract = "Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VDLD) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [3H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apo VLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are sepaeated by polyacrylamide gel electrophoresis. Similar patterns are noted when nonrecirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.",
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Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats. / Noel, S. P.; Wong, L.; Dolphin, P. J.; Dory, Ladislav; Rubenstein, D.

In: Unknown Journal, Vol. 64, No. 2, 01.01.1979, p. 674-683.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats

AU - Noel, S. P.

AU - Wong, L.

AU - Dolphin, P. J.

AU - Dory, Ladislav

AU - Rubenstein, D.

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N2 - Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VDLD) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [3H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apo VLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are sepaeated by polyacrylamide gel electrophoresis. Similar patterns are noted when nonrecirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.

AB - Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VDLD) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [3H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apo VLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are sepaeated by polyacrylamide gel electrophoresis. Similar patterns are noted when nonrecirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.

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DO - 10.1172/JCI109508

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JF - Unknown Journal

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