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首页> 外文期刊>Cell discovery. >Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRα+ adipose progenitors
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Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRα+ adipose progenitors

机译：维甲酸通过增加脂肪血管和诱导PDGFRα + 脂肪祖细胞的米色脂肪生成来诱导白色脂肪组织褐变

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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.
机译：在白色脂肪组织中形成米色脂肪细胞会增加能量消耗，这是减少肥胖症和预防代谢症状的一种有前途的策略。维生素A及其生物活性代谢产物视黄酸（RA）在脂质代谢中具有调节作用。在这里，我们报道RA通过激活血管内皮生长因子（VEGF）信号诱导白色脂肪组织褐变。 RA通过VEGFA / VEGFR2信号传导触发血管生成，并引发血小板源性生长因子受体α阳性（PDGFRα + ）脂肪前体细胞的新生。另外，RA促进了体外毛细血管网络形成米色/棕色脂肪细胞的形成。使用PDGFRα追踪小鼠，我们发现血管系统通过包含PDGFRα + 祖细胞而成为脂肪形成库，PDGFRα + 祖细胞在RA或VEGF164处理下分化为米色脂肪细胞。 VEGF受体的条件性基因敲除可阻断RA刺激的白色脂肪组织褐变。此外，VEGFA和RA激活p38MAPK以增强RA受体与Prdm16启动子的RA反应元件的结合并上调Prdm16转录。总之，RA通过增加脂肪血管和促进PDGFRα + 脂肪祖细胞的米色脂肪生成而诱导白色脂肪组织褐变。

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