期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 12, 页码 6883-6889出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1920419117
关键词
BCL6; sympathetic nervous system; thermogenesis; development; metabolism
资金
- NIH [DK094641, DK101064]
- Agency for Science, Technology, and Research (A*STAR, Singapore) National Science Scholarship
- Dermatology Foundation Dermatologist Investigator Research Fellowship
- American Heart Association (AHA) [18PRE34080250, 16PRE26960008]
Adipose tissue provides a defense against starvation and environmental cold. These dichotomous functions are performed by three distinct cell types: energy-storing white adipocytes, and thermogenic beige and brown adipocytes. Previous studies have demonstrated that exposure to environmental cold stimulates the recruitment of beige adipocytes in the white adipose tissue (WAT) of mice and humans, a process that has been extensively investigated. However, beige adipose tissue also develops during the peri-weaning period in mice, a developmental program that remains poorly understood. Here, we address this gap in our knowledge using genetic, imaging, physiologic, and genomic approaches. We find that, unlike cold-induced recruitment in adult animals, peri-weaning development of beige adipocytes occurs in a temperature- and sympathetic nerve-independent manner. Instead, the transcription factor B cell leukemia/lymphoma 6 (BCL6) acts in a cell-autonomous manner to regulate the commitment but not the maintenance phase of beige adipogenesis. Genome-wide RNA-sequencing (seq) studies reveal that BCL6 regulates a core set of genes involved in fatty acid oxidation and mitochondrial uncoupling, which are necessary for development of functional beige adipocytes. Together, our findings demonstrate that distinct transcriptional and signaling mechanisms control peri-weaning development and cold-induced recruitment of beige adipocytes in mammals.
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