Adipose tissue is a key determinant of whole body metabolism and energy homeostasis. Unraveling the regulatory mechanisms underlying adipogenesis is therefore highly relevant from a biomedical perspective. Our current understanding of fat cell differentiation is centered on the transcriptional cascades driven by the C/EBP protein family and the master regulator PPARγ. To elucidate further components of the adipogenic gene regulatory network, we performed a large-scale transcription factor (TF) screen overexpressing 734 TFs in mouse pre-adipocytes and probed their effect on differentiation. We identified 23 novel pro-adipogenic TFs and characterized the top ranking TF, ZEB1, as being essential for adipogenesis both in vitro and in vivo. Moreover, its expression levels correlate with fat cell differentiation potential in humans. Genomic profiling further revealed that this TF directly targets and controls the expression of most early and late adipogenic regulators, identifying ZEB1 as a central transcriptional component of fat cell differentiation.
Animal experimentation: All animal experiments were conducted in strict accordance with Swiss law and all experiments were approved by the ethics commission of the state veterinary office (60/2012, 43/2011).
Human subjects: The work on obese subjects was approved by the ethics committee at the University Hospital of Heidelberg and is conforming to the ethical guidelines of the 2000 Helsinki declaration. All participants provided witnessed written informed consent prior entering the study (S-365/2007). The trial was registered as NCT00773565.
- Peter Tontonoz, University of California, Los Angeles, United States
© 2014, Gubelmann et al.
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