Tonello C, Giordano A, Cozzi V, Cinti S, Stock M J, Carruba M O, Nisoli E
Centre for Study and Research on Obesity, Department of Pharmacology, School of Medicine, LITA Vialba, L. Sacco Hospital, Milan University, Italy.
FEBS Lett. 1999 Jan 15;442(2-3):167-72. doi: 10.1016/s0014-5793(98)01627-5.
The thermogenic activity of brown adipose tissue (BAT) is heavily dependent on high perfusion, through its dense vascular system. Angiogenesis must go hand-in-hand with BAT functions, but little is known about the factors controlling it. In the present study we demonstrate that: (a) vascular endothelial growth factor (VEGF) is synthesised and released in brown adipocytes in culture; (b) VEGF mRNA isoforms and protein appear in dispersed mature brown adipocytes and whole tissue; (c) VEGF expression is increased in BAT from cold-exposed rats, and in cultured brown adipocytes exposed to noradrenaline and the beta3-adrenoceptor agonists; (e) BAT from genetically obese (falfa) rats exhibits reduced expression of VEGF as well as a change in the ratio of mRNA isoforms. It is concluded that sympathetic control of VEGF expression via noradrenaline acting on beta3-adrenoceptors plays a major role in developmental and adaptive angiogenesis, and defects in this contribute to the reduced thermogenic capacity of BAT in genetic obesity.
棕色脂肪组织（BAT）的产热活性高度依赖于通过其密集血管系统实现的高灌注。血管生成必须与BAT功能协同进行，但对于控制血管生成的因素却知之甚少。在本研究中，我们证明：（a）血管内皮生长因子（VEGF）在培养的棕色脂肪细胞中合成并释放；（b）VEGF mRNA亚型和蛋白质出现在分散的成熟棕色脂肪细胞和整个组织中；（c）冷暴露大鼠的BAT中以及暴露于去甲肾上腺素和β3 -肾上腺素能受体激动剂的培养棕色脂肪细胞中，VEGF表达增加；（e）遗传性肥胖（苜蓿）大鼠的BAT表现出VEGF表达降低以及mRNA亚型比例的变化。得出的结论是，去甲肾上腺素作用于β3 -肾上腺素能受体对VEGF表达的交感神经控制在发育性和适应性血管生成中起主要作用，而这方面的缺陷导致遗传性肥胖中BAT产热能力降低。
