Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI110835

Regulation of Hepatic Lipoprotein Receptors in the Dog. RAPID REGULATION OF APOLIPOPROTEIN B,E RECEPTORS, BUT NOT OF APOLIPOPROTEIN E RECEPTORS, BY INTESTINAL LIPOPROTEINS AND BILE ACIDS

Bo Angelin, Carol A. Raviola, Thomas L. Innerarity, and Robert W. Mahley

Gladstone Foundation Laboratories for Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco, California 94140

Department of Pathology, University of California, San Francisco, California 94140

Department of Medicine, University of California, San Francisco, California 94140

Find articles by Angelin, B. in: PubMed | Google Scholar

Gladstone Foundation Laboratories for Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco, California 94140

Department of Pathology, University of California, San Francisco, California 94140

Department of Medicine, University of California, San Francisco, California 94140

Find articles by Raviola, C. in: PubMed | Google Scholar

Gladstone Foundation Laboratories for Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco, California 94140

Department of Pathology, University of California, San Francisco, California 94140

Department of Medicine, University of California, San Francisco, California 94140

Find articles by Innerarity, T. in: PubMed | Google Scholar

Gladstone Foundation Laboratories for Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco, California 94140

Department of Pathology, University of California, San Francisco, California 94140

Department of Medicine, University of California, San Francisco, California 94140

Find articles by Mahley, R. in: PubMed | Google Scholar

Published April 1, 1983 - More info

Published in Volume 71, Issue 4 on April 1, 1983
J Clin Invest. 1983;71(4):816–831. https://doi.org/10.1172/JCI110835.
© 1983 The American Society for Clinical Investigation
Published April 1, 1983 - Version history
View PDF
Abstract

Two distinct lipoprotein receptors can be expressed in the dog liver. One is the apolipoprotein (apo-) B,E receptor. This receptor binds apo-B-containing low density lipoproteins (LDL), as well as apo-E-containing lipoproteins, such as the cholesterol-induced high density lipoproteins (HDLc). The second hepatic lipoprotein receptor is the apo-E receptor. It binds apo-E HDLc and chylomicron remnants, but not LDL. The present studies were undertaken to determine whether short-term (acute) regulation of the two receptors can occur in response to perturbations in hepatic cholesterol metabolism. The design used three groups of experimental animals: (a) immature dogs (with both hepatic apo-B,E and apo-E receptors expressed), (b) adult dogs (with predominantly the apo-E receptor expressed and little detectable apo-B,E receptor binding activity), and (c) dogs treated with the bile acid sequestrant cholestyramine or those that have undergone biliary diversion (with apo-E receptors and induced apo-B,E receptors).

In the first series of experiments, changes in hepatic lipoprotein receptor expression were studied by delivering cholesterol to the liver via intestinal lymph lipoproteins. Dog lymph (5-11 mg of triglycerides/min per kg of body weight, 0.15-0.3 mg of cholesterol/min per kg) or saline were infused intravenously for 6-8 h into matched pairs of dogs. Serial liver biopsies were obtained at intervals of 1-2 h. A progressive loss of specific (calcium-dependent) binding of LDL was seen in hepatic membranes from both immature and cholestyramine-treated dogs. After 4-6 h of lymph infusion, almost no apo-B,E receptor binding could be detected. The decrease in binding of apo-E HDLc to the same membranes was much less pronounced, and could be explained by a loss of binding of HDLc to the apo-B,E receptor; there was little or no effect on apo-E receptor binding.

In the second series of experiments, the effects of a diminished hepatic demand for cholesterol on lipoprotein receptor expression were studied by suppressing bile acid synthesis. The bile acid taurocholate (2-3 μmol/kg per min) was infused intravenously over a 6-h interval. This resulted in a progressive loss of LDL binding to liver membranes of immature or cholestyramine-treated dogs. The infusion of taurocholate for 6 h did not significantly alter the expression of the apo-E receptor binding activity, whereas apo-B,E receptor activity was rapidly down-regulated. Preparation of a bile fistula in adult dogs markedly induced the expression of the apo-B,E receptor. In this state, the binding activity of the apo-B,E receptor could be almost totally abolished by reinfusion of taurocholate for 6 h, without profoundly affecting apo-E receptor binding. Evidence from the analysis of plasma lipoprotein patterns and tissue culture reactivity suggested that changes in assayed hepatic lipoprotein receptor activity occurred in concert with changes in plasma lipoproteins.

The results indicate that the two canine hepatic lipoprotein receptors differ in their metabolic regulation. The apo-B,E receptor responds rapidly to changes in hepatic requirements for cholesterol. The apo-E receptor appears to be more refractory to acute regulation. The rapidity of the changes in the activity of the apo-B,E receptor (within 2-4 h) suggests that the binding activity of this receptor may be regulated by factors independent of protein synthesis.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 816
page 816
icon of scanned page 817
page 817
icon of scanned page 818
page 818
icon of scanned page 819
page 819
icon of scanned page 820
page 820
icon of scanned page 821
page 821
icon of scanned page 822
page 822
icon of scanned page 823
page 823
icon of scanned page 824
page 824
icon of scanned page 825
page 825
icon of scanned page 826
page 826
icon of scanned page 827
page 827
icon of scanned page 828
page 828
icon of scanned page 829
page 829
icon of scanned page 830
page 830
icon of scanned page 831
page 831
Version history
  • Version 1 (April 1, 1983): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts