BCL6 regulates brown adipocyte dormancy to maintain thermogenic reserve and fitness.

Brown adipocytes provide a metabolic defense against environmental cold but become dormant as mammals habituate to warm environments. Although dormancy is a regulated response in brown adipocytes to environmental warmth, its transcriptional mechanisms and functional importance are unknown. Here, we identify B cell leukemia/lymphoma 6 (BCL6) as a critical regulator of dormancy in brown adipocytes but not for their commitment, differentiation, or cold-induced activation. In a temperature-dependent manner, BCL6 suppresses apoptosis, fatty acid storage, and coupled respiration to maintain thermogenic fitness during dormancy. Mechanistically, BCL6 remodels the epigenome of brown adipocytes to enforce brown and oppose white adipocyte cellular identity. Thus, unlike other thermogenic regulators, BCL6 is specifically required for maintaining thermogenic fitness when mammals acclimate to environmental warmth.