PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1

Patricia C Chui ¹, Hong-Ping Guan , Michael Lehrke

⁰Division 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.

The Journal of Clinical Investigation +

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July 12, 2005

View abstract on PubMed

Summary

Antidiabetic drugs called thiazolidinediones (TZDs) increase oxidized LDL receptor 1 (OLR1) in fat cells. This enhances cholesterol and fatty acid uptake, potentially improving insulin sensitivity.

Area Of Science

Biochemistry
Cell Biology
Endocrinology

Background

Adipose tissue stores energy and accumulates cholesterol.
Cholesterol and triglyceride levels are linked within adipocytes, but regulatory mechanisms are unclear.

Purpose Of The Study

To investigate how antidiabetic drugs influence cholesterol metabolism in adipocytes.
To identify novel targets of the nuclear receptor PPARgamma in fat cells.

Main Methods

Utilized cultured mouse adipocytes and adenoviral gene delivery.
Assessed OLR1 gene regulation by PPARgamma ligands.
Measured oxidized LDL (oxLDL) uptake and lipid content.

Main Results

Thiazolidinediones (TZDs) upregulate oxidized LDL receptor 1 (OLR1) in adipocytes by altering OLR1 gene coactivator/corepressor exchange.
TZDs increase oxLDL uptake into adipocytes, dependent on OLR1.
Enhanced OLR1 expression augments adipocyte cholesterol and fatty acid uptake.
OLR1 expression is elevated in obesity and induced by PPARgamma ligands in vivo.
TZD treatment reduced serum oxLDL levels in diabetic animals.

Conclusions

Identified OLR1 as a novel PPARgamma target gene in adipocytes.
OLR1 induction by PPARgamma ligands may mediate lipid metabolism and insulin sensitivity regulation in adipocytes.

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