Centripetal cholesterol flux from extrahepatic organs to the liver is independent of the concentration of high density lipoprotein-cholesterol in plasma

Yasunori Osono, Laura A. Woollett, Keith R. Marotti, George W. Melchior, John M. Dietschy

Research output: Contribution to journalArticle

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Abstract

High density lipoproteins (HDLs) play a role in two processes that include the amelioration of atheroma formation and the centripetal flow of cholesterol from the extrahepatic organs to the liver. This study tests the hypothesis that the flow of sterol from the peripheral organs to the liver is dependent upon circulating HDL concentrations. Transgenic C57BL/6 mice were used that expressed variable amounts of simian cholesteryl ester-transfer protein (CETP). The rate of centripetal cholesterol flux was quantitated as the sum of the rates of cholesterol synthesis and low density lipoprotein- cholesterol uptake in the extrahepatic tissues. Steady-state concentrations of cholesterol carried in HDL (HDL-C) varied from 59 to 15 mg/dl and those of apolipoprotein A1 from 138 to 65 mg/dl between the control mice (CETP(c)) and those maximally expressing the transfer protein (CETP+). There was no difference in the size of the extrahepatic cholesterol pools in the CETP(c) and CETP+ animals. Similarly, the rates of cholesterol synthesis (83 and 80 mg/day per kg, respectively) and cholesterol carried in low density lipoprotein uptake (4 and 3 mg/day per kg, respectively) were virtually identical in the two groups. Thus, under circumstances where the steady- state concentration of HDL-C varied 4-fold, the centripetal flux of cholesterol from the peripheral organs to the liver was essentially constant at ≃87 mg/day per kg. These studies demonstrate that neither the concentration of HDL-C or apolipoprotein A1 nor the level of CETP activity dictates the magnitude of centripetal cholesterol flux from the extrahepatic organs to the liver, at least in the mouse.

Original languageEnglish (US)
Pages (from-to)4114-4119
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number9
DOIs
StatePublished - Apr 30 1996

Fingerprint

HDL Cholesterol
Cholesterol Ester Transfer Proteins
Cholesterol
HDL Lipoproteins
Liver
Apolipoprotein A-I
Sterols
Atherosclerotic Plaques
Inbred C57BL Mouse
LDL Lipoproteins
LDL Cholesterol
Transgenic Mice

Keywords

  • high density lipoprotein-cholesterol transport

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Centripetal cholesterol flux from extrahepatic organs to the liver is independent of the concentration of high density lipoprotein-cholesterol in plasma. / Osono, Yasunori; Woollett, Laura A.; Marotti, Keith R.; Melchior, George W.; Dietschy, John M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 9, 30.04.1996, p. 4114-4119.

Research output: Contribution to journalArticle

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