Angiogenesis plays an instrumental role in the modulation of adipose tissue mass and metabolism. Targeting adipose vasculature provides an outstanding opportunity for treatment of obesity and metabolic disorders. Here, we report the physiological functions of VEGFR1 in the modulation of adipose angiogenesis, obesity, and global metabolism. Pharmacological inhibition and genetic deletion of endothelial VEGFR1 augmented adipose angiogenesis and browning of subcutaneous white adipose tissue, leading to elevated thermogenesis. In a diet-induced obesity model, endothelial-VEGFR1 deficiency demonstrated a potent anti-obesity effect by improving global metabolism. Along with metabolic changes, fatty liver and insulin sensitivity were also markedly improved in VEGFR1-deficient high fat diet (HFD)–fed mice. Together, our data indicate that targeting of VEGFR1 provides an exciting new opportunity for treatment of obesity and metabolic diseases, such as liver steatosis and type 2 diabetes.

血管生成在调节脂肪组织质量和代谢中起重要作用。靶向脂肪脉管系统提供了治疗肥胖症和代谢紊乱的绝佳机会。在这里，我们报告了VEGFR1在调节脂肪血管生成，肥胖和整体代谢中的生理功能。内皮VEGFR1的药理抑制和基因删除会增加脂肪血管生成和皮下白色脂肪组织褐变，从而导致生热升高。在饮食诱发的肥胖模型中，内皮-VEGFR1缺乏症通过改善整体代谢表现出有效的抗肥胖作用。随着新陈代谢的变化，在缺乏VEGFR1的高脂饮食（HFD）喂养的小鼠中，脂肪肝和胰岛素敏感性也得到了显着改善。一起，