BBA Mol Cell Biol l-Transcriptional brakes on the road to adipocyte thermogenesis.pdf

White adipocytes represent the principle site for energy storage whereas brown/beige adipocytes emerge fromseemingly distinct cellular lineages and burn chemical energy to produce heat. Thermogenic adipocytes utilizecell-type selective master regulatory transcription factors to drive the expression of their adipocyte thermogenicgene program. White adipocytes harbor transcriptional mechanisms to suppress the thermogenic gene programand maintain an energy-storing function. Here, we summarize some of the key developmental and transcriptionalmechanisms 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 highlighta number of recent studies, including our own work on the transcription factor, ZFP423, that illustrate thepotential to engineer the subcutaneous and visceral white fat lineages to adopt a thermogenic fat cell fate byreleasing the inhibition of the adipocyte thermogenic gene program. These transcriptional brakes on adipocytethermogenesis may represent potential targets of therapeutic interventions designed to combat obesity andassociated metabolic disorders.