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FOXP4 differentially controls cold-induced beige adipocyte differentiation and thermogenesis

Fuhua Wang,Shuqin Xu,T. Chen,Shifeng Ling,Wei Zhang,Shaojiao Wang,Rujiang Zhou,X. Xia,Zhengju Yao,Pengxiao Li,Xiaodong Zhao,Ji-qiu Wang,Xizhi Guo

Published 2021 in bioRxiv

ABSTRACT

Beige adipocytes possess a discrete developmental origin and notable plasticity in thermogenic capacity in response to various environmental cues. But the transcriptional machinery controlling beige adipocyte development and thermogenesis remains largely unknown. By analyzing beige adipocyte-specific knockout mice, we identified a transcription factor, Forkhead Box P4 (FOXP4) that differentially governs beige adipocyte differentiation and activation. Depletion of Foxp4 caused a decline in the frequency of beige preadipocytes by switching their cell fate towards fibroblastic cells at the expense of beige adipocytes. However, we observed that ablation of Foxp4 in differentiated adipocytes profoundly potentiated their thermogenesis upon cold exposure. Of note, the outcome of Foxp4-deficiency on UCP1-mediated thermogenesis was confined to beige adipocytes, rather than to brown adipocytes. Taken together, we submit that FOXP4 primes beige adipocyte cell fate commitment and differentiation by potent transcriptional repression of the thermogenic program.

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