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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Shao, M; Ishibashi, J; Kusminski, CM; Wang, QA; Hepler, C; Vishvanath, L; MacPherson, KA; Spurgin, SB; Sun, K; Holland, WL; Seale, P; Gupta, RK

Published Date

  • June 14, 2016

Published In

Volume / Issue

  • 23 / 6

Start / End Page

  • 1167 - 1184

PubMed ID

  • 27238639

Pubmed Central ID

  • PMC5091077

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2016.04.023


  • eng

Conference Location

  • United States