来自瑞典斯德哥尔摩大学，卡洛林斯卡医学院，北京大学分子医学研究院等处的研究人员就脂肪组织代谢与血管新生相关的分子机制这一未知的领域进行了研究，发现了一种新机制，对于脂肪代谢研究以及血管新生研究意义重大，并且也从理论上说明可以应用血管新生调控元件来治疗肥胖和代谢失调症。

体内脂肪细胞的代谢过程是一个非常活跃、从不间断的循环过程。正常情况下，机体内的脂肪细胞一方面不断地从血液中摄取食物分解后产生的游离脂肪酸，另一方面脂肪细胞内生成的磷酸三酰甘油又可被体内的脂肪酶催化分解成甘油和游离脂肪酸，后者中的一部分被重新释放人血液，供机体其他组织利用，另一部分则又被重新酯化。

这个生化过程目前科学家们了解的比较清楚，但是具体脂肪组织代谢与血管新生相关的分子机制仍然是属于这一领域的一个研究空白，在这篇文章中，研究人员将小鼠曝露在冷环境下，刺激白色脂肪细胞和棕色脂肪细胞的活性，并从实验结果中发现了一种新调控机制。

研究人员发现冷刺激会导致棕色脂肪相关蛋白，比如uncoupling protein-1 (UCP1)和PGC-1a的表达水平增加，同时VEGF等血管新生因子（Proangiogenic factors）也会增多，而内生性血管新生抑制子，比如血小板反应蛋白（thrombospondin）等则表达量会降低。野生型的小鼠在冷刺激下，脂肪组织会发生低氧现象，而UCP1－/ －小鼠则不会出现这种情况，有意思的是，VEGFR2阻断能消除这种血管新生，并极大的伤害非战栗产热（nonshivering）量。而且研究人员还发现VEGFR1阻断会导致相反的作用：增加脂肪的血管新生，以及非战栗产热量。

这些研究结果从理论上说明可以应用血管新生调控元件来治疗肥胖和代谢失调症。

推荐原始出处：

Cell Metabolism, 99-109, 7 January 2009 doi:10.1016/j.cmet.2008.11.009

Hypoxia-Independent Angiogenesis in Adipose Tissues during Cold Acclimation

Yuan Xue1,Natasa Petrovic2,Renhai Cao1,Ola Larsson3,Sharon Lim1,Shaohua Chen1,Helena M. Feldmann2,Zicai Liang4,Zhenping Zhu5,Jan Nedergaard2,Barbara Cannon2andYihai Cao1,,

1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden
2 The Wenner-Gren Institute, the Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden
3 Department of Biochemistry, McGill University, 3655 Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada
4 Institute of Molecular Medicine, Peking University, Beijing 100871, China
5 ImClone Systems Incorporated, 108 Varick Street, New York, NY 10014, USA

Summary

The molecular mechanisms of angiogenesis in relation to adipose tissue metabolism remain poorly understood. Here, we show that exposure of mice to cold led to activation of angiogenesis in both white and brown adipose tissues. In the inguinal depot, cold exposure resulted in elevated expression levels of brown-fat-associated proteins, including uncoupling protein-1 (UCP1) and PGC-1. Proangiogenic factors such as VEGF were upregulated, and endogenous angiogenesis inhibitors, including thrombospondin, were downregulated. In wild-type mice, the adipose tissues became hypoxic during cold exposure; in UCP1/ mice, hypoxia did not occur, but, remarkably, the augmented angiogenesis was unaltered and was thus hypoxia independent. Intriguingly, VEGFR2 blockage abolished the cold-induced angiogenesis and significantly impaired nonshivering thermogenesis capacity. Unexpectedly, VEGFR1 blockage resulted in the opposite effects: increased adipose vascularity and nonshivering thermogenesis capacity. Our findings have conceptual implications concerning application of angiogenesis modulators for treatment of obesity and metabolic disorders.