BCL6 regulates brown adipocyte dormancy to maintain thermogenic reserve and fitness
| Autor: | Vassily I. Kutyavin, Ajay Chawla |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Physiology
Brown Adipocytes Acclimatization Regulator acclimation Biology Epigenesis Genetic Mice 03 medical and health sciences 0302 clinical medicine Functional importance hemic and lymphatic diseases Animals White Adipocytes 030304 developmental biology 0303 health sciences Multidisciplinary Fatty Acids brown fat Thermogenesis Epigenome Biological Sciences BCL6 Cell biology Cold Temperature Adipocytes Brown PNAS Plus Proto-Oncogene Proteins c-bcl-6 Dormancy transcription metabolism 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1907308116 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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