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PMID: 16007265 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1.

The Journal of clinical investigation ·Vol. 115 ·No. 8 ·2005-08-00 ·Pages 2244-56

Chui PC, Guan HP, Lehrke M, Lazar MA

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 PPARgamma 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 PPARgamma 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 PPARgamma 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 PPARgamma ligands regulate lipid metabolism and insulin sensitivity in adipocytes.

MeSH Terms
Adipocytes/metabolism Animals Cells, Cultured Cholesterol/metabolism Fatty Acids/metabolism Gene Expression Regulation/drug effects Hypoglycemic Agents/pharmacology Insulin Resistance Lipoproteins, LDL/metabolism Mice PPAR gamma/metabolism Receptors, LDL/biosynthesis Receptors, Oxidized LDL Scavenger Receptors, Class E Thiazolidinediones/pharmacology
Chemicals
Fatty Acids Hypoglycemic Agents Lipoproteins, LDL Olr1 protein, mouse PPAR gamma Receptors, LDL Receptors, Oxidized LDL Scavenger Receptors, Class E Thiazolidinediones oxidized low density lipoprotein Cholesterol
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chui Patricia C
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149, USA.
Guan Hong-Ping
Lehrke Michael
Lazar Mitchell A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI24130
Published
2005-08-00
Epub
2005-00-07
Pages
2244-56
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1172230
Subset
IM
Grants
NIDDK NIH HHS · P30 DK019525 · United States
NIDDK NIH HHS · R01 DK049780 · United States
NIDDK NIH HHS · DK19525 · United States
NIDDK NIH HHS · R01 DK49780 · United States
External Links
PubMed source DOI: 10.1172/JCI24130 PMC Full Text View journal details
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