Transcriptional brakes on the road to adipocyte thermogenesis.

White adipocytes represent the principle site for energy storage whereas brown/beige adipocytes emerge from seemingly distinct cellular lineages and burn chemical energy to produce heat. Thermogenic adipocytes utilize cell-type selective master regulatory transcription factors to drive the expression of their adipocyte thermogenic gene program. White adipocytes harbor transcriptional mechanisms to suppress the thermogenic gene program and maintain an energy-storing function. Here, we summarize some of the key developmental and transcriptional mechanisms leading to the postnatal recruitment of thermogenic adipocytes under physiological conditions, with a particular emphasis on the transcriptional "brakes" on the thermogenic gene program. We highlight a number of recent studies, including our own work on the transcription factor, ZFP423, that illustrate the potential to engineer the subcutaneous and visceral white fat lineages to adopt a thermogenic fat cell fate by releasing the inhibition of the adipocyte thermogenic gene program. These transcriptional brakes on adipocyte thermogenesis may represent potential targets of therapeutic interventions designed to combat obesity and associated metabolic disorders.