Back to Search
Start Over
The adipocyte clock controls brown adipogenesis via TGF-β/BMP signaling pathway
- Source :
- Journal of Cell Science.
- Publication Year :
- 2015
- Publisher :
- The Company of Biologists, 2015.
-
Abstract
- The molecular clock is intimately linked with metabolic regulation and brown adipose tissue plays a key role in energy homeostasis. However, whether the cell-intrinsic clock machinery participates in brown adipocyte development is unknown. Here we show that Bmal1, the essential clock transcription activator, inhibits brown adipogenesis to adversely impact brown fat formation and thermogenic capacity. Global ablation of Bmal1 in mice increases brown fat mass and cold tolerance, while adipocyte-selective inactivation of Bmal1 recapitulates these effects and demonstrates its cell-autonomous role in brown adipocyte formation. Further loss- and gain-of function studies in mesenchymal precursors and committed brown progenitors reveal that Bmal1 inhibits brown adipocyte lineage commitment and terminal differentiation. Mechanistically, Bmal1 inhibits brown adipogenesis through direct transcriptional control of key components of the TGF-β pathway together with reciprocally altered BMP signaling, and activation of TGF-β, or blockade of BMP pathways, suppresses enhanced differentiation in Bmal1-deficient brown adipocytes. Collectively, our study demonstrates a novel temporal regulatory mechanism in fine-tuning brown adipocyte lineage progression to impact brown fat formation and thermogenic regulation, which may be targeted therapeutically to combat obesity.
- Subjects :
- Regulation of gene expression
endocrine system
medicine.medical_specialty
biology
Cell Biology
Transforming growth factor beta
Bone morphogenetic protein
ARNTL
chemistry.chemical_compound
medicine.anatomical_structure
Endocrinology
chemistry
Adipogenesis
Internal medicine
Adipocyte
Brown adipose tissue
medicine
biology.protein
Thermogenesis
Subjects
Details
- ISSN :
- 14779137 and 00219533
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Science
- Accession number :
- edsair.doi...........73c4d428b37d1838fbd190ad412d5384
- Full Text :
- https://doi.org/10.1242/jcs.167643