Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • 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
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
PPARγ regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1
Patricia C. Chui, … , Michael Lehrke, Mitchell A. Lazar
Patricia C. Chui, … , Michael Lehrke, Mitchell A. Lazar
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2244-2256. https://doi.org/10.1172/JCI24130.
View: Text | PDF
Research Article Metabolism

PPARγ regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1

  • Text
  • PDF
Abstract

In addition to its role in energy storage, adipose tissue also accumulates cholesterol. Concentrations of cholesterol and triglycerides are strongly correlated in the adipocyte, but little is known about mechanisms regulating cholesterol metabolism in fat cells. Here we report that antidiabetic thiazolidinediones (TZDs) and other ligands for the nuclear receptor PPARγ dramatically upregulate oxidized LDL receptor 1 (OLR1) in adipocytes by facilitating the exchange of coactivators for corepressors on the OLR1 gene in cultured mouse adipocytes. TZDs markedly stimulate the uptake of oxidized LDL (oxLDL) into adipocytes, and this requires OLR1. Increased OLR1 expression, resulting either from TZD treatment or adenoviral gene delivery, significantly augments adipocyte cholesterol content and enhances fatty acid uptake. OLR1 expression in white adipose tissue is increased in obesity and is further induced by PPARγ ligand treatment in vivo. Serum oxLDL levels are decreased in both lean and obese diabetic animals treated with TZDs. These data identify OLR1 as a novel PPARγ target gene in adipocytes. While the physiological role of adipose tissue in cholesterol and oxLDL metabolism remains to be established, the induction of OLR1 is a potential means by which PPARγ ligands regulate lipid metabolism and insulin sensitivity in adipocytes.

Authors

Patricia C. Chui, Hong-Ping Guan, Michael Lehrke, Mitchell A. Lazar

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
OLR1
 is induced by PPARγ ligands in 3T3 L1 adipocytes. (A) Comparison o...
OLR1 is induced by PPARγ ligands in 3T3 L1 adipocytes. (A) Comparison of OLR1 and aP2 mRNA levels in 3T3-L1 preadipocytes (Pread), adipocytes treated with vehicle (DMSO), and rosiglitazone-treated adipocytes (Rosi). (B) Quantitation of OLR1 compared with CD36 mRNA induction by rosiglitazone, using real-time PCR. Results are normalized to mRNA levels in vehicle-treated adipocytes. Data expressed as mean ± SEM (n = 4). (C) Rosiglitazone induces OLR1 protein expression in 3T3-L1 adipocytes according to Western blot analysis. Histone deacetylase 2 (HDAC2) protein levels show equal loading. (D) Rosiglitazone (500 nM or 1 μM for 4 days) induces OLR1 mRNA expression in human adipocytes. Real-time PCR results expressed as mean ± SEM (n = 4). hOLR1, human OLR1. (E) Dose response for OLR1 induction by rosiglitazone and the non-TZD PPARγ ligand GW7845. (F) Induction of OLR1 by rosiglitazone (100 nM) is blocked by the PPARγ antagonist PD068235 (PD; 50 μM). rRNA, ribosomal RNA.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts