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Significance 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 brown adipocytes. Mechanistically, BCL6 drives a gene expression program that promotes survival, fatty acid oxidation, and uncoupled respiration. Thus, unlike other transcription factors that regulate cold-induced thermogenesis, BCL6 is specifically required for maintaining thermogenic fitness during adaptation to environmental warmth.

BCL6 regulates brown adipocyte dormancy to maintain thermogenic reserve and fitness