[Studies on growth of brown adipose tissue by means of cell culture and angiogenesis in vitro techniques].

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.