Diverse intra-cellular control mechanisms of nonshivering thermogenesis. -The roles of glucagon and beta_3 agonist.

为了阐明非寒战产热的主要部位褐色脂肪组织（BAT）的产热机制，研究了不同条件下去甲肾上腺素（NA）、胰高血糖素(G)和β -3肾上腺素能激动剂（BRL37344:BRL）对BAT体内和体外产热活性的影响，得到如下结果。1. 连续几代的冷适应大鼠具有较高的非寒战产热能力，但与冷适应大鼠（CA）相比，它们似乎在较少的能量消耗下适应寒冷。2. 雌性大鼠在体内和体外产热能力均与雄性大鼠相同。3. 在CA中，急性冷暴露后，gdp与BAT线粒体的结合明显高，尽管在静息状态下与WC没有区别。而间歇性冷暴露大鼠（ICE）在这两种情况下均显著高于WC。4. 尽管在体内具有较高的产热能力，但在体外，BAT的产热活性在CA中受到抑制，可能是通过对camp后信号系统的某种抑制。NA、G和BRL的作用无显著性差异。5. 脂解与BAT耗氧量增加之间的正相关关系仅在ICE中观察到。6. 长期给药NA，而不给药G，模拟了BAT对上述药物的体外产热反应。7. IP_3刺激新生儿早期BAT的产热作用。8. 甲状腺功能减退时，BAT对异丙肾上腺素、G和BRL的反应受到抑制。9. 这些结果表明，在不同的条件下，BAT的产热能力会发生不同的改变，G刺激BAT产热的部分途径是通过IP_3途径，而棕色脂肪细胞的产热活性可以在冷驯化条件下被抑制，从而防止持续NA刺激下的过度劳累。

In order to clarify the thermogenic mechanisms of brown adipose tissue (BAT),main site of nonshivering thermogenesis (NST), the effects of noradrenaline (NA), glucagon (G) and beta-3 adrenergic agonist (BRL37344:BRL) on in vivo and in vitro thermogenic activities of BAT under various conditions were examined and the following results were obtained. 1. Cold-adapted rats for successive generations had high nonshivering thermogenic capacity,but they seem to be adapted to cold under less energy expenditure compared with cold-acclimated rats(CA). 2. Female rats had same thermogenic capacities as male ones in both criteria of in vivo and in vitro. 3. In CA, GDP-binding to BAT mitochondria was significantly high after acute cold exposure, although it was not different from WC in the resting state. While those in intermittently cold-exposed rats (ICE) were significantly high than those of WC in the both conditions. 4. In spite of the high thermogenic capacities in vivo, the in vitro BAT themogenic activity was suppressed in CA, possibly through some inhibition(s) on the post-cAMP signalling system. There were no differences among the effects of NA, G and BRL. 5. The positive relationship between lipolysis and increase in oxygen consumption of BAT was observed only in ICE. 6. Chronic administration of NA, but not of G, simulated the in vitro BAT responses to thermogenic the above agents. 7. IP_3 stimulated thermogenesis in BAT of the early stage of neonatal life. 8. The responses of BAT to isoprenaline, G and BRL were suppressed under hypothyroidism. 9. These results indicate that BAT thermogenic capacity could be modified differently under different conditions, that G stimulates BAT thermogenesis, in part, via IP_3 route, and that the thermogenic activity of brown adipocyte could be suppressed under cold acclimation, provably to prevent overworking under continuous NA stimulation.