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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1997-3-6
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pubmed:abstractText |
Recent studies indicate that a peroxisome proliferator-activated receptor, PPAR gamma, functions as an important adipocyte determination factor. In contrast, tumor necrosis factor-alpha (TNF alpha) inhibits adipogenesis, causes dedifferentiation of mature adipocytes, and reduces the expression of several adipocyte-specific genes. Here, we report that treatment of 3T3-L1 adipocytes with TNF alpha resulted in a time- and concentration-dependent decrease in PPAR gamma mRNA expression to the level detected in preadipocytes. PPAR gamma mRNA levels were reduced by 95% with 3 nM TNF alpha treatment for 24 h. Half-maximal effects were seen after 3 h treatment with 3 nM TNF alpha or with 50 pM TNF alpha (24-h exposure). Parallel reductions in PPAR gamma protein levels were also observed after treatment of 3T3-L1 adipocytes with TNF alpha. Using a ribonuclease protection assay, both alternatively spliced PPAR gamma isoforms (gamma 1 and gamma 2) were shown to be negatively regulated by TNF alpha. The down-regulation of PPAR gamma by TNF-alpha preceded the diminution in expression of other adipocyte-specific genes including CCAAT/enhancer binding protein and adipocyte fatty acid-binding protein (aP2). The effect of TNF alpha was specific for the gamma-isoform of PPARs, since the expression of PPAR delta mRNA was not affected by treatment with TNF alpha. Low level constitutive expression of PPAR gamma in 3T3-L1 adipocytes (at levels approximately 2- to 3-fold higher than in preadipocytes) partially blocked the inhibitory effect of TNF alpha on aP2 and adipsin expression. These findings support the following conclusions: 1) PPAR gamma expression is necessary for the maintenance of the adipocyte phenotype. 2) PPAR gamma, but not PPAR delta, expression is sufficient to attenuate TNF alpha-mediated effects on adipocyte phenotype. 3) Reduced PPAR gamma gene expression is likely to represent an important component of the mechanism by which TNF alpha exerts its antiadipogenic effects.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Complement Factor D,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fabp5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fabp7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myelin P2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/complement factor D, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1457-66
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8923470-3T3 Cells,
pubmed-meshheading:8923470-Adipocytes,
pubmed-meshheading:8923470-Animals,
pubmed-meshheading:8923470-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:8923470-Carrier Proteins,
pubmed-meshheading:8923470-Cell Differentiation,
pubmed-meshheading:8923470-Cells, Cultured,
pubmed-meshheading:8923470-Complement Factor D,
pubmed-meshheading:8923470-DNA-Binding Proteins,
pubmed-meshheading:8923470-Dose-Response Relationship, Drug,
pubmed-meshheading:8923470-Down-Regulation,
pubmed-meshheading:8923470-Fatty Acid-Binding Proteins,
pubmed-meshheading:8923470-Gene Expression Regulation,
pubmed-meshheading:8923470-Mice,
pubmed-meshheading:8923470-Myelin P2 Protein,
pubmed-meshheading:8923470-Neoplasm Proteins,
pubmed-meshheading:8923470-Nerve Tissue Proteins,
pubmed-meshheading:8923470-Nuclear Proteins,
pubmed-meshheading:8923470-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:8923470-Serine Endopeptidases,
pubmed-meshheading:8923470-Suppression, Genetic,
pubmed-meshheading:8923470-Time Factors,
pubmed-meshheading:8923470-Transcription Factors,
pubmed-meshheading:8923470-Tumor Necrosis Factor-alpha
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pubmed:year |
1996
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pubmed:articleTitle |
Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha.
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pubmed:affiliation |
Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
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pubmed:publicationType |
Journal Article
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