Ueno N, Nakamura K, Yamashita H, Kizaki T, Ookawara T, Ohno H
Department of Hygiene, Showa University School of Medicine, Tokyo, Japan.
Nihon Eiseigaku Zasshi. 1994 Feb;48(6):1058-66. doi: 10.1265/jjh.48.1058.
To elucidate the mechanism of brown adipose tissue (BAT) enlargement, we investigated the effects of norepinephrine (NE) and insulin on the in vitro growth of rat brown adipose cells (RBAC) and the capillary growth in angiogenesis in vitro using co-culture of bovine capillary endothelial cells (BCEC) and rat smooth muscle cells. In the primary cell culture, NE significantly enhanced the growth of RBAC in the range of 10(-9)-10(-5)M, whereas it did not stimulate the growth of BCEC. Insulin showed the same trend. Moreover, both NE and insulin appeared to increase the expression of mRNA for basic fibroblast growth factor (bFGF), which is a potent angiogenic factor, in RBAC. At 4 h after NE stimulation, the bFGF mRNA expression was considerably increased but it decreased markedly after 16 h. These results suggest that the bFGF mRNA expression in RBAC is quickly simulated by NE, wih resulting bFGF production. Actually, bFGF stimulated the RBAC growth up to about 170% of the control level. However, neither NE nor insulin stimulated the expression of the bFGF gene in BCEC. On the other hand, NE notably increased the capillary growth in vitro compared with insulin. It is thus possible that NE and insulin contribute to the growth of RBAC and endothelial cells partly through bFGF production by an autocrine mechanism, suggesting that both agonists play an important role not only in the thermogenic function of BAT but also in BAT enlargement.
为阐明棕色脂肪组织（BAT）增大的机制，我们使用牛毛细血管内皮细胞（BCEC）与大鼠平滑肌细胞共培养的方法，研究了去甲肾上腺素（NE）和胰岛素对大鼠棕色脂肪细胞（RBAC）体外生长以及体外血管生成中毛细血管生长的影响。在原代细胞培养中，NE在10^(-9)-10^(-5)M范围内显著促进RBAC的生长，而对BCEC的生长无刺激作用。胰岛素也呈现相同趋势。此外，NE和胰岛素似乎均能增加RBAC中碱性成纤维细胞生长因子（bFGF，一种强效血管生成因子）的mRNA表达。NE刺激4小时后，bFGF mRNA表达显著增加，但16小时后明显下降。这些结果表明，NE能快速刺激RBAC中bFGF mRNA的表达，进而产生bFGF。实际上，bFGF可将RBAC的生长刺激至对照水平的约170%。然而，NE和胰岛素均未刺激BCEC中bFGF基因的表达。另一方面，与胰岛素相比，NE显著增加了体外毛细血管的生长。因此，NE和胰岛素可能部分通过自分泌机制产生bFGF，从而促进RBAC和内皮细胞的生长，这表明这两种激动剂不仅在BAT的产热功能中发挥重要作用，而且在BAT增大过程中也起重要作用。
