Charon C, Dupuy F, Marie V, Bazin R
Institut National de la Santé et de la Recherche Médicale, U177, Paris, France.
Am J Physiol. 1995 Jun;268(6 Pt 1):E1039-45. doi: 10.1152/ajpendo.1995.268.6.E1039.
This study was undertaken to determine whether administration of a thermogenic beta-agonist drug to Zucker fatty rats could correct some of the earliest metabolic defects detectable in brown adipose tissue (BAT). Fa/fa and fa/fa littermates were given oral administration of BRL-35135 from 8 to 16 days of age. In fa/fa rats, the lipid content of white and brown adipose tissues was significantly reduced. In the BAT of fa/fa rats, thermogenic capacity was restored to the level observed in Fa/fa rats, whereas hyperactivity of fatty acid synthetase was abolished, and a deficit in lipoprotein lipase (activity and mRNA) was partly corrected. Hyperinsulinemia in fa/fa pups was significantly reduced. The decreased content of GLUT-4 mRNA that characterized BAT of fa/fa pups was also restored to normal. At variance with observations in preobese rats, BRL had very little or no effect on lean Fa/fa rats. The present study reveals that chronic administration of a beta-agonist drug early in life prevents emergence of most of the metabolic abnormalities that characterize fa/fa rats at the onset of obesity. This suggests that impaired sympathetic activity may play a role in the development of this genetic obesity.
本研究旨在确定给 Zucker 肥胖大鼠施用一种产热β-肾上腺素能激动剂药物是否能够纠正棕色脂肪组织（BAT）中可检测到的一些最早的代谢缺陷。在 8 至 16 日龄时，给 fa/fa 大鼠及其同窝的 fa/fa 幼崽口服 BRL-35135。在 fa/fa 大鼠中，白色和棕色脂肪组织的脂质含量显著降低。在 fa/fa 大鼠的 BAT 中，产热能力恢复到 Fa/fa 大鼠中观察到的水平，脂肪酸合成酶的过度活跃被消除，脂蛋白脂肪酶（活性和 mRNA）的缺陷得到部分纠正。fa/fa 幼崽的高胰岛素血症显著降低。fa/fa 幼崽 BAT 中特征性的 GLUT-4 mRNA 含量降低也恢复正常。与对肥胖前期大鼠的观察结果不同，BRL 对瘦的 Fa/fa 大鼠几乎没有影响或没有影响。本研究表明，在生命早期长期施用β-肾上腺素能激动剂药物可预防肥胖开始时 fa/fa 大鼠所具有的大多数代谢异常的出现。这表明交感神经活动受损可能在这种遗传性肥胖的发展中起作用。
