來自瑞典斯德哥爾摩大學,，卡洛林斯卡醫(yī)學院,，北京大學分子醫(yī)學研究院等處的研究人員就脂肪組織代謝與血管新生相關的分子機制這一未知的領域進行了研究，發(fā)現(xiàn)了一種新機制,，對于脂肪代謝研究以及血管新生研究意義重大,，并且也從理論上說明可以應用血管新生調(diào)控元件來治療肥胖和代謝失調(diào)癥。
體內(nèi)脂肪細胞的代謝過程是一個非?；钴S,、從不間斷的循環(huán)過程。正常情況下，機體內(nèi)的脂肪細胞一方面不斷地從血液中攝取食物分解后產(chǎn)生的游離脂肪酸,，另一方面脂肪細胞內(nèi)生成的磷酸三酰甘油又可被體內(nèi)的脂肪酶催化分解成甘油和游離脂肪酸,，后者中的一部分被重新釋放人血液，供機體其他組織利用,，另一部分則又被重新酯化,。
這個生化過程目前科學家們了解的比較清楚，但是具體脂肪組織代謝與血管新生相關的分子機制仍然是屬于這一領域的一個研究空白,，在這篇文章中，研究人員將小鼠曝露在冷環(huán)境下,，刺激白色脂肪細胞和棕色脂肪細胞的活性,，并從實驗結果中發(fā)現(xiàn)了一種新調(diào)控機制。
研究人員發(fā)現(xiàn)冷刺激會導致棕色脂肪相關蛋白,，比如uncoupling protein-1 (UCP1)和PGC-1a的表達水平增加,，同時VEGF等血管新生因子（Proangiogenic factors）也會增多，而內(nèi)生性血管新生抑制子,，比如血小板反應蛋白（thrombospondin）等則表達量會降低,。野生型的小鼠在冷刺激下，脂肪組織會發(fā)生低氧現(xiàn)象,，而UCP1－/ －小鼠則不會出現(xiàn)這種情況,，有意思的是，VEGFR2阻斷能消除這種血管新生,，并極大的傷害非戰(zhàn)栗產(chǎn)熱（nonshivering）量,。而且研究人員還發(fā)現(xiàn)VEGFR1阻斷會導致相反的作用：增加脂肪的血管新生，以及非戰(zhàn)栗產(chǎn)熱量,。
這些研究結果從理論上說明可以應用血管新生調(diào)控元件來治療肥胖和代謝失調(diào)癥,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
