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

非颤抖产热的多种细胞内控制机制。

基本信息

批准号：
03670072
负责人：
YAHATA Takehiro
金额：
$ 1.28万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670072/
关键词：
brown adipose tissue nonshivering thermogenesis glucagon BRL37344 inositol triphosphate tissue oxygen consumption GDP binding cold adapted rat for successive generations 褐色脂肪組織寒冷馴化組織細片酸素消費量ノルアドレナリンサイクリックAMP

项目摘要

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.

为了阐明非颤抖性产热（NST）的主要部位--棕色脂肪组织（BAT）的产热机制，研究了去甲肾上腺素（NA）、胰高血糖素（G）和β 3肾上腺素能激动剂（BRL 37344：BRL）在不同条件下对BAT体内和体外产热活性的影响。1.连续几代的冷适应大鼠具有较高的非颤抖产热能力，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冷。2.雌性大鼠在体内和体外产热能力与雄性大鼠相同。3.在CA，GDP结合BAT线粒体是显着高急性冷暴露后，虽然它是从WC在静息状态下没有什么不同。而间歇冷暴露大鼠（ICE）在这两种条件下均显著高于WC。4.尽管体内产热能力高，但CA中的体外BAT产热活性受到抑制，这可能是通过对cAMP后信号传导系统的一些抑制。NA、G和BRL的作用无差异。5.脂肪分解与BAT耗氧量增加之间的正相关关系仅在ICE中观察到。6.慢性给药NA，而不是G，模拟在体外BAT的反应，产热上述代理。7. IP_3刺激新生儿早期BAT产热。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，在不同条件下，BAT的产热能力受到不同程度的调节，G通过IP_3途径促进BAT的产热，冷驯化可抑制棕色脂肪细胞的产热活性，从而防止NA刺激下的过度工作。