CM-Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program.pdf Mengle Shao Jeff Ishibashi Christine M. Kusminski Qiong Wang Chelsea Hepler Lavanya Vishvanath Karen A. MacPherson Stephen Spurgin Kai Sun William Holland Patrick Seale Rana Gupta 10.25376/hra.7800740.v1 https://hra.figshare.com/articles/journal_contribution/CM-Zfp423_Maintains_White_Adipocyte_Identity_through_Suppression_of_the_Beige_Cell_Thermogenic_Gene_Program_pdf/7800740 <div>The transcriptional regulators Ebf2 and Prdm16</div><div>establish and maintain the brown and/or beige fat</div><div>cell identity. However, the mechanisms operating in</div><div>white adipocytes to suppress the thermogenic gene</div><div>program and maintain an energy-storing phenotype</div><div>are less understood. Here, we report that the transcriptional</div><div>regulator Zfp423 is critical for maintaining</div><div>white adipocyte identity through suppression of the</div><div>thermogenic gene program. Zfp423 expression is</div><div>enriched in white versus brown adipocytes and suppressed</div><div>upon cold exposure. Doxycycline-inducible</div><div>inactivation of Zfp423 in mature adipocytes, combined</div><div>with b-adrenergic stimulation, triggers a</div><div>conversion of differentiated adiponectin-expressing</div><div>inguinal and gonadal adipocytes into beige-like adipocytes;</div><div>this reprogramming event is sufficient to</div><div>prevent and reverse diet-induced obesity and insulin</div><div>resistance. Mechanistically, Zfp423 acts in adipocytes</div><div>to inhibit the activity of Ebf2 and suppress</div><div>Prdm16 activation. These data identify Zfp423 as a</div><div>molecular brake on adipocyte thermogenesis and</div><div>suggest a therapeutic strategy to unlock the thermogenic</div><div>potential of white adipocytes in obesity.</div> 2019-03-04 22:01:42 Zfp423 Beige adipocyte White adipocytes Ebf2 Cell Biology