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IGFBP-3, hypoxia and TNF-alpha inhibit adiponectin transcription.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2009 May 15; Vol. 382 (4), pp. 785-9. Date of Electronic Publication: 2009 Mar 24. - Publication Year :
- 2009
-
Abstract
- The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-gamma, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin. It activates PPAR-gamma-RXR-alpha heterodimers bound to PPAR-gamma response elements in the adiponectin promoter. Rosiglitazone-stimulated adiponectin protein synthesis in 3T3-L1 mouse adipocytes has been shown to be inhibited by IGFBP-3, which can be induced by hypoxia and the proinflammatory cytokine, TNF-alpha, two inhibitors of adiponectin transcription. The present study demonstrates that IGFBP-3, the hypoxia-mimetic agent cobalt chloride, and TNF-alpha inhibit rosiglitazone-induced adiponectin transcription in mouse embryo fibroblasts that stably express PPAR-gamma2. Native IGFBP-3 can bind RXR-alpha and inhibited rosiglitazone stimulated promoter activity, whereas an IGFBP-3 mutant that does not bind RXR-alpha did not. These results suggest that IGFBP-3 may mediate the inhibition of adiponectin transcription by hypoxia and TNF-alpha, and that IGFBP-3 binding to RXR-alpha may be required for the observed inhibition.
- Subjects :
- 3T3-L1 Cells
Adiponectin antagonists & inhibitors
Animals
Cell Hypoxia
Cobalt pharmacology
Fibroblasts drug effects
Fibroblasts metabolism
Genes, Reporter
Humans
Hypoglycemic Agents pharmacology
Mice
Obesity metabolism
PPAR gamma agonists
Retinoid X Receptor alpha agonists
Retinoid X Receptor alpha metabolism
Rosiglitazone
Thiazolidinediones pharmacology
Tumor Necrosis Factor-alpha pharmacology
Adiponectin genetics
Insulin Resistance genetics
Insulin-Like Growth Factor Binding Protein 3 metabolism
PPAR gamma metabolism
Transcription, Genetic drug effects
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 382
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 19324019
- Full Text :
- https://doi.org/10.1016/j.bbrc.2009.03.112