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Publication : Distinct signaling and transcriptional pathways regulate peri-weaning development and cold-induced recruitment of beige adipocytes.

First Author  Wu Y Year  2020
Journal  Proc Natl Acad Sci U S A Volume  117
Issue  12 Pages  6883-6889
PubMed ID  32139607 Mgi Jnum  J:286577
Mgi Id  MGI:6402667 Doi  10.1073/pnas.1920419117
Citation  Wu Y, et al. (2020) Distinct signaling and transcriptional pathways regulate peri-weaning development and cold-induced recruitment of beige adipocytes. Proc Natl Acad Sci U S A 117(12):6883-6889
abstractText  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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