Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRα+ adipose progenitors
| Autor: | Min Du, Zhixiu Wang, Junxing Zhao, Xing Fu, Liang Zhao, Bo Wang, Qiyu Tian, Xingwei Liang, Mei-Jun Zhu, Noe Alberto Gomez, Sophie C. Trombetta, Jeanene M Deavila |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
PRDM16 medicine.medical_specialty Adipose tissue macrophages Retinoic acid Adipose tissue Cell Biology White adipose tissue Biochemistry 03 medical and health sciences chemistry.chemical_compound Vascular endothelial growth factor A 030104 developmental biology Endocrinology Growth factor receptor chemistry Adipogenesis Internal medicine Genetics medicine Molecular Biology |
| Zdroj: | Cell Discovery. 3 |
| ISSN: | 2056-5968 |
| DOI: | 10.1038/celldisc.2017.36 |
| Popis: | Formation of beige adipocytes within white adipose tissue enhances energy expenditure, which is a promising strategy to reduce obesity and prevent metabolic symptoms. Vitamin A and its bioactive metabolite, retinoic acid (RA), have regulatory roles in lipid metabolism. Here we report that RA induces white adipose tissue browning via activating vascular endothelial growth factor (VEGF) signaling. RA triggered angiogenesis and elicited de novo generation of platelet-derived growth factor receptor α positive (PDGFRα+) adipose precursor cells via VEGFA/VEGFR2 signaling. In addition, RA promoted beige/brown adipocyte formation from capillary networks in vitro. Using PDGFRα tracking mice, we found that the vascular system acted as an adipogenic repository by containing PDGFRα+ progenitors which differentiated into beige adipocytes under RA or VEGF164 treatments. Conditional knockout of VEGF receptors blocked RA-stimulated white adipose tissue browning. Moreover, the VEGFA and RA activated p38MAPK to enhance the binding of RA receptor to RA response elements of the Prdm16 promoter and upregulated Prdm16 transcription. In conclusion, RA induces white adipose tissue browning by increasing adipose vascularity and promoting beige adipogenesis of PDGFRα+ adipose progenitors. |
| Databáze: | OpenAIRE |
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