UCSF

During exposure to environmental cold, brown adipocytes protect against hypothermia by generating heat (thermogenesis). In warm environments, brown adipocytes become inactive or dormant, but still maintain their identity and thermogenic capacity, allowing rapid reactivation of thermogenesis upon subsequent cold exposure. Our understanding of the dormant state and its regulation is very limited. Here, we show that the transcription factor B cell leukemia/lymphoma 6 (BCL6) is specifically required for maintenance of thermogenic capacity during dormancy in mouse brown adipocytes. By a combination of both direct and indirect transcriptional mechanisms, BCL6 promotes uncoupled respiration, fatty acid oxidation, and survival in dormant brown adipocytes. In part, BCL6 achieves this by remodeling the epigenome of brown adipocytes to enforce brown and oppose white adipocyte cellular identity. Thus, unlike other transcription factors that regulate cold-induced thermogenesis, BCL6 is specifically required for maintenance of thermogenic fitness during adaptation to environmental warmth.