Divergent effects of peroxisome proliferator-activated receptor γ agonists and tumor necrosis factor α on adipocyte ApoE expression

Lili Yue, Neda Rasouli, Gouri Ranganathan, Philip A. Kern, Theodore Mazzone

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


ApoE is expressed in multiple mammalian cell types in which it supports cellular differentiated function. In this report we demonstrate that apoE expression in adipocytes is regulated by factors involved in modulating systemic insulin sensitivity. Systemic treatment with pioglitazone increased systemic insulin sensitivity and increased apoE mRNA levels in adipose tissue by 2-3-fold. Treatment of cultured 3T3-L1 adipocytes with ciglitazone increased apoE mRNA levels by 2-4-fold in a dose-dependent manner and increased apoE secretion from cells. Conversely, treatment of adipocytes with tumor necrosis factor (TNF) α reduced apoE mRNA levels and apoE secretion by 60%. Neither insulin nor a peroxisome proliferator-activated receptor (PPAR) α agonist regulated adipocyte apoE gene expression. In addition, treatment of human monocyte-derived macrophages with ciglitazone did not regulate expression of apoE. Additional analyses using reporter genes indicated that the effect of TNFα and PPARγ agonists on the apoE gene was mediated via distinct gene control elements. The TNFα effect was mediated by elements within the proximal promoter, whereas the PPARγ effect was mediated by elements within a downstream enhancer. However, the addition of TNFα substantially reduced the absolute levels of apoE reporter gene response even in the presence of ciglitazone. These results indicate for the first time that adipose tissue expression of apoE is modulated by physiologic regulators of insulin sensitivity.

Original languageEnglish
Pages (from-to)47626-47632
Number of pages7
JournalJournal of Biological Chemistry
Issue number46
StatePublished - Nov 12 2004

Bibliographical note

Copyright 2008 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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