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
Defective HDL particle uptake in ob/ob hepatocytes causes decreased recycling, degradation, and selective lipid uptake
David L. Silver, … , Nan Wang, Alan R. Tall
David L. Silver, … , Nan Wang, Alan R. Tall
Published January 15, 2000
Citation Information: J Clin Invest. 2000;105(2):151-159. https://doi.org/10.1172/JCI8087.
View: Text | PDF
Article

Defective HDL particle uptake in ob/ob hepatocytes causes decreased recycling, degradation, and selective lipid uptake

  • Text
  • PDF
Abstract

Levels of plasma HDL are determined in part by catabolism in the liver. However, it is unclear how the hepatic catabolism of holo-HDL is regulated or mediated. Recently, we found that ob/ob mice have defective liver catabolism of HDL apoproteins in vivo that can be reversed by low-dose leptin treatment. Here we examined HDL catabolism and trafficking at the cellular level using isolated hepatocytes. We demonstrate that ob/ob hepatocytes have reduced binding, association, degradation, and resecretion of HDL apoproteins and 50% less selective lipid uptake relative to wild-type hepatocytes. In addition, HDL apoproteins were found to colocalize with transferrin in the general endosomal recycling compartment (ERC) in wild-type hepatocytes. However, the localization to the ERC was markedly reduced in ob/ob hepatocytes. Filipin staining of cellular cholesterol revealed decreased cholesterol in the ERC in ob/ob hepatocytes. Defects in HDL cell association and cholesterol distribution were reversed by leptin administration. The findings show a major defect in HDL uptake and recycling in ob/ob hepatocytes and suggest that HDL recycling through the ERC plays a role in the determination of plasma HDL protein and cholesterol levels.

Authors

David L. Silver, Nan Wang, Alan R. Tall

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Analysis of HDL cholesteryl ether and free cholesterol uptake during HDL...
Analysis of HDL cholesteryl ether and free cholesterol uptake during HDL recycling. Triple-labeled apoE-free human HDL (3H cholesteryl ether, 14C free cholesterol, 125I) was incubated with both ob/ob and wild-type hepatocytes according to the pulse-chase scheme used in Figure 1c. (a) Shown is the HDL protein concentrations that remained inside the cells, or was secreted intact, or degraded at the end of the chase period (ob/ob versus WT, *P < 0.001). (b) The amount of cholesteryl ether and free cholesterol per nanogram of HDL protein that remained inside the cells or was secreted at the end of the chase period is shown. (c) Apparent selective uptake was measured by subtracting the amount of HDL cholesteryl ether (3H) or free cholesterol (14C) from the amount of HDL protein (125I) that remained inside the cells at the end of the chase period. Results were reported as specific internalization (cell), degradation, and secretion by subtracting the counts remaining after incubations with 100-fold excess unlabeled HDL. All experiments were performed twice, in triplicate, with similar results.

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

Sign up for email alerts