Format

Send to

Choose Destination
Cell Metab. 2016 Jun 14;23(6):1167-1184. doi: 10.1016/j.cmet.2016.04.023. Epub 2016 May 26.

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

Author information

1
Touchstone Diabetes Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2
Institute for Diabetes, Obesity and Metabolism and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Touchstone Diabetes Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: rana.gupta@utsouthwestern.edu.

Abstract

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 β-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.

PMID:
27238639
PMCID:
PMC5091077
DOI:
10.1016/j.cmet.2016.04.023
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflicting interests statement. The authors declare that they have no competing financial interests.

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center