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Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program.

Authors: Shao, Mengle  Ishibashi, Jeff  Kusminski, Christine M  Wang, Qiong A  Hepler, Chelsea  Vishvanath, Lavanya  MacPherson, Karen A  Spurgin, Stephen B  Sun, Kai  Holland, William L  Seale, Patrick  Gupta, Rana K 
Citation: Shao M, etal., Cell Metab. 2016 Jun 14;23(6):1167-1184. doi: 10.1016/j.cmet.2016.04.023. Epub 2016 May 26.
Pubmed: (View Article at PubMed) PMID:27238639
DOI: Full-text: DOI:10.1016/j.cmet.2016.04.023

The transcriptional regulators Ebf2 and Prdm16 establish and maintain the brown and/or beige fat cell identity. However, the mechanisms operating in white adipocytes to suppress the thermogenic gene program and maintain an energy-storing phenotype are less understood. Here, we report that the transcriptional regulator Zfp423 is critical for maintaining white adipocyte identity through suppression of the thermogenic gene program. Zfp423 expression is enriched in white versus brown adipocytes and suppressed upon cold exposure. Doxycycline-inducible inactivation of Zfp423 in mature adipocytes, combined with ß-adrenergic stimulation, triggers a conversion of differentiated adiponectin-expressing inguinal and gonadal adipocytes into beige-like adipocytes; this reprogramming event is sufficient to prevent and reverse diet-induced obesity and insulin resistance. Mechanistically, Zfp423 acts in adipocytes to inhibit the activity of Ebf2 and suppress Prdm16 activation. These data identify Zfp423 as a molecular brake on adipocyte thermogenesis and suggest a therapeutic strategy to unlock the thermogenic potential of white adipocytes in obesity.


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RGD Object Information
RGD ID: 13673839
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.