Transcriptional control of preadipocyte determination by Zfp423

Rana K Gupta, Zoltan Arany, Patrick Seale, Rina J. Mepani, Li Ye, Heather M. Conroe, Yang A. Roby, Heather Kulaga, Randall R. Reed, Bruce M. Spiegelman

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

The worldwide epidemic of obesity has increased the urgency to develop a deeper understanding of physiological systems related to energy balance and energy storage, including the mechanisms controlling the development of fat cells (adipocytes). The differentiation of committed preadipocytes to adipocytes is controlled by PPARγ and several other transcription factors, but the molecular basis for preadipocyte determination is not understood. Using a new method for the quantitative analysis of transcriptional components, we identified the zinc-finger protein Zfp423 as a factor enriched in preadipose versus non-preadipose fibroblasts. Ectopic expression of Zfp423 in non-adipogenic NIH 3T3 fibroblasts robustly activates expression of Pparg in undifferentiated cells and permits cells to undergo adipocyte differentiation under permissive conditions. Short hairpin RNA (shRNA)-mediated reduction of Zfp423 expression in 3T3-L1 cells blunts preadipocyte Pparg expression and diminishes the ability of these cells to differentiate. Furthermore, both brown and white adipocyte differentiation is markedly impaired in Zfp423-deficient mouse embryos. Zfp423 regulates Pparg expression, in part, through amplification of the BMP signalling pathway, an effect dependent on the SMAD-binding capacity of Zfp423. This study identifies Zfp423 as a transcriptional regulator of preadipocyte determination.

Original languageEnglish (US)
Pages (from-to)619-623
Number of pages5
JournalNature
Volume464
Issue number7288
DOIs
StatePublished - Mar 25 2010

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Adipocytes
Fibroblasts
White Adipocytes
Brown Adipocytes
3T3-L1 Cells
Peroxisome Proliferator-Activated Receptors
Zinc Fingers
Small Interfering RNA
Transcription Factors
Embryonic Structures
Obesity
Proteins

ASJC Scopus subject areas

  • General

Cite this

Gupta, R. K., Arany, Z., Seale, P., Mepani, R. J., Ye, L., Conroe, H. M., ... Spiegelman, B. M. (2010). Transcriptional control of preadipocyte determination by Zfp423. Nature, 464(7288), 619-623. https://doi.org/10.1038/nature08816

Transcriptional control of preadipocyte determination by Zfp423. / Gupta, Rana K; Arany, Zoltan; Seale, Patrick; Mepani, Rina J.; Ye, Li; Conroe, Heather M.; Roby, Yang A.; Kulaga, Heather; Reed, Randall R.; Spiegelman, Bruce M.

In: Nature, Vol. 464, No. 7288, 25.03.2010, p. 619-623.

Research output: Contribution to journalArticle

Gupta, RK, Arany, Z, Seale, P, Mepani, RJ, Ye, L, Conroe, HM, Roby, YA, Kulaga, H, Reed, RR & Spiegelman, BM 2010, 'Transcriptional control of preadipocyte determination by Zfp423', Nature, vol. 464, no. 7288, pp. 619-623. https://doi.org/10.1038/nature08816
Gupta RK, Arany Z, Seale P, Mepani RJ, Ye L, Conroe HM et al. Transcriptional control of preadipocyte determination by Zfp423. Nature. 2010 Mar 25;464(7288):619-623. https://doi.org/10.1038/nature08816
Gupta, Rana K ; Arany, Zoltan ; Seale, Patrick ; Mepani, Rina J. ; Ye, Li ; Conroe, Heather M. ; Roby, Yang A. ; Kulaga, Heather ; Reed, Randall R. ; Spiegelman, Bruce M. / Transcriptional control of preadipocyte determination by Zfp423. In: Nature. 2010 ; Vol. 464, No. 7288. pp. 619-623.
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