Inhibitor of DNA Binding 2 Is a Small Molecule-Inducible Modulator of Peroxisome Proliferator-Activated Receptor-γ Expression and Adipocyte Differentiation
Open Access
- 1 September 2008
- journal article
- other
- Published by The Endocrine Society in Molecular Endocrinology
- Vol. 22 (9), 2038-2048
- https://doi.org/10.1210/me.2007-0454
Abstract
We previously identified the small molecule harmine as a regulator of peroxisome proliferator activated-receptor γ (PPARγ) and adipocyte differentiation. In an effort to identify signaling pathways mediating harmine’s effects, we performed transcriptional profiling of 3T3-F442A preadipocytes. Inhibitor of DNA biding 2 (Id2) was identified as a gene rapidly induced by harmine but not by PPARγ agonists. Id2 is also induced in 3T3-L1 preadipocytes treated with dexamethasone, 3-isobutyl-1-methylxanthine, and insulin, suggesting that Id2 regulation is a common feature of the adipogenic program. Stable overexpression of Id2 in preadipocytes promotes expression of PPARγ and enhances morphological differentiation and lipid accumulation. Conversely, small interfering RNA-mediated knockdown of Id2 antagonizes adipocyte differentiation. Mice lacking Id2 expression display reduced adiposity, and embryonic fibroblasts derived from these mice exhibit reduced PPARγ expression and a diminished capacity for adipocyte differentiation. Finally, Id2 expression is elevated in adipose tissues of obese mice and humans. These results outline a role for Id2 in the modulation of PPARγ expression and adipogenesis and underscore the utility of adipogenic small molecules as tools to dissect adipocyte biology.Keywords
This publication has 29 references indexed in Scilit:
- Transcriptional regulator Id2 mediates CD8+ T cell immunityNature Immunology, 2006
- Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genesDiabetologia, 2005
- Role of Krüppel-like Factor 15 (KLF15) in Transcriptional Regulation of AdipogenesisJournal of Biological Chemistry, 2005
- Krox20 stimulates adipogenesis via C/EBPβ-dependent and -independent mechanismsCell Metabolism, 2005
- Krüppel-like transcription factor KLF5 is a key regulator of adipocyte differentiationCell Metabolism, 2005
- The Krüppel-like Factor KLF2 Inhibits Peroxisome Proliferator-activated Receptor-γ Expression and AdipogenesisJournal of Biological Chemistry, 2003
- Inhibition of Adipogenesis by Wnt SignalingScience, 2000
- Id helix–loop–helix proteins inhibit nucleoprotein complex formation by the TCF ETS-domain transcription factorsThe EMBO Journal, 1999
- ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.Genes & Development, 1996
- Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factorCell, 1994