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

为了阐明棕色脂肪组织(BAT)的生热机制，研究了去甲肾上腺素(NA)、高血糖素(G)和β-3肾上腺素能激动剂(BRL37344：BRL)在不同条件下对BAT的体内外生热活性的影响。1.连续代冷适应大鼠具有较高的非颤抖生热能力，但与冷适应大鼠(CA)相比，冷适应大鼠似乎在较少的能量消耗下适应了冷。2.无论在体内还是体外，雌性大鼠与雄性大鼠都具有相同的生热能力。3.急性冷暴露后，CA与BAT线粒体的GDP结合率显著升高，但与WC在静息状态下的结合无明显差异。而间歇性冷暴露大鼠(ICE)在两种情况下均显著高于WC组。4.尽管在体内具有较高的生热能力，但CA的体外BAT生热活性受到抑制，可能是通过对cAMP后信号系统的抑制(S)。NA、G和BRL的作用差异无统计学意义。5.只有在ICE中才能观察到BAT的脂肪分解与氧耗量的增加呈正相关。6.长期给予NA，而不是G，模拟体外BAT对上述致热物质的反应。7.IP_3刺激新生儿生命早期BAT的产热。8.甲减状态下，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的生热能力可能有不同的变化，G部分通过IP_3途径刺激BAT的生热，冷驯化可以抑制棕色脂肪细胞的生热活性，这可能是为了防止在持续的NA刺激下过度工作。

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.