Tumor necrosis factor-induced reversal of adipocytic phenotype of 3T3-L1 cells is preceded by a loss of nuclear CCAAT/enhancer binding protein (C/EBP)

David Ron, Allan R. Brasier, Robert E. McGehee, Joel F. Habener

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-treated 3T3-L1 adipocytes were used as a model for studying the effects of systemic inflammation on adipose tissue. Lipopolysaccharide-treated monocyteconditioned medium or recombinant human TNFα induced morphological dedifferentiation of the adipocytes and led to loss of adipocyte specific gene expression. Gel shift. Southwestern and Western immunoblot analysis demonstrated that dedifferentiation was preceded by a decrease in the DNA binding activity and protein level of the transcription factor CCAAT/enhancer binding protein (C/EBP). Liver activating protein a related protein that binds identical DNA sequences increased during ntokine treatment. Both proteins activate specific enhancer elements located in the promoter region of many genes whose transcription is altered during systemic inflammation. Pulsechase labeling followed by immunoprecipitation demonstrated ihat C/EBP is a rapidly turning over protein in adipocytes and that cytokine treatment led to a specific time dependent deiTease in its rate of synthesis. Because C/EBP binding sites have been shown to play an important role in regulating the expression of genes involved in adipocyte metabolism we propose that the TNF-induced changes in the complement of transcription factors binding those sites may be important in the pathogenesis of inflammation-induced atrophy of adipose tissue.

Original languageEnglish (US)
Pages (from-to)223-233
Number of pages11
JournalJournal of Clinical Investigation
Volume89
Issue number1
StatePublished - 1992

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CCAAT-Enhancer-Binding Proteins
3T3-L1 Cells
Nuclear Proteins
Adipocytes
Tumor Necrosis Factor-alpha
Phenotype
Inflammation
Adipose Tissue
Proteins
Transcription Factors
Binding Sites
Gene Expression
DNA-Binding Proteins
Immunoprecipitation
Genetic Promoter Regions
Protein Binding
Atrophy
Lipopolysaccharides
Western Blotting
Gels

Keywords

  • Acute phase
  • Adipocytes
  • Cachexia
  • Cytokines

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tumor necrosis factor-induced reversal of adipocytic phenotype of 3T3-L1 cells is preceded by a loss of nuclear CCAAT/enhancer binding protein (C/EBP). / Ron, David; Brasier, Allan R.; McGehee, Robert E.; Habener, Joel F.

In: Journal of Clinical Investigation, Vol. 89, No. 1, 1992, p. 223-233.

Research output: Contribution to journalArticle

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