CLARIFICATION OF CONTROL MECHANISM OF NONSHIVERING THERMOGENESIS BY ANALYSIS OF GENE INFORMATION AND INTRACELLULAR SIGNAL TRANSDACTION SYSTEM

基因信息和细胞内信号传导系统分析阐明非颤抖生热的控制机制

• 批准号: 09670083
• 负责人: YAHATA Takehiro
• 金额: $ 2.11万
• 依托单位: NAYORO CITY COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670083/
• 关键词: nonshivering thermogenesis; brown adipose tissue; glucagon; noradrenaline; Ca; FOK rat; prolactin; prolactin receptor mRNA; 組織酸素消費量; プロラクチン受容体発現mRNA; PCR; 寒冷馴化; 組織血流量; 尾部皮膚温

Brown adipose tissue (BAT), the major site of nonshivering thermogenesis, plays important roles in metabolic temperature regulation. The present study was done to clarify the role of glucagon and its control mechanism on BAT function, and the following results were obtained.(1) In Ca-treated rat, noradrenaline (NA)-induced increases in TィイD2BATィエD2 and TィイD2colィエD2 were small as compared to control rat. While TィイD2tailィエD2 was increased in Ca-treated rat, but decreased in control by NA. It is suggested that Ca suppresses NA-induced thermogenesis in BAT as well as constriction of peripheral blood vessels. The effects of glucagon were not different between Ca-treated rat and control one.(2) Food intake of the inbred heat-tolerant, as well as cold-tolerant, FOK rat did not differ from that of Std : Wistar rat in both warm-acclimated and cold-acclimated conditions.(3) In cold-acclimated FOK rat, NA-induced increase in oxygen consumption was larger than those of control strains. Glucagon-induced increase in Tcol was also larger in FOK rat.(4) Plasma glucagon levels after acute cold exposure were higher in both warm-acclimated and cold-acclimated FOK rat than control strains.(5) ECィイD250ィエD2 of BAT to glucagon was smaller in FOK rat as compared to Std : Wistar one.(6) Inositol-triphosphate(IPィイD23ィエD2) increased oxygen consumption of BAT of neonatal rat dose-dependently.(7) Prolactin (PRL) treatment decreased the thermogenic response of BAT to glucagon.(8) PCR analysis demonstrated signals of PRL-receptor mRNA in BAT. The signal of short form PRL-receptor mRNA was stronger than that of long form one, and this signal was stronger in neonatal BAT than adult's one.These result suggest that glucagon plays an important role in enhansment of nonshivering thermogenesis of the inbred heat-tolerant, as well as cold-tolerant, FOK rat, and that glucagon stimulates BAT thermogenic activity via IPィイD23ィエD2-CaィイD12+ィエD1 route and this route is inhibitedly regulated by PRL.

棕色脂肪组织（BAT）是非颤抖性产热的主要部位，在代谢性温度调节中起重要作用。本研究旨在阐明胰高血糖素对BAT功能的作用及其调控机制，并获得以下结果。(1)在Ca处理的大鼠中，去甲肾上腺素（NA）诱导的T淋巴细胞D2 BAT淋巴细胞D2和T淋巴细胞D2 col淋巴细胞D2的增加与对照大鼠相比较小。Ca处理组大鼠T淋巴细胞D_2、尾淋巴细胞D_2增加，NA处理组大鼠T淋巴细胞D_2、尾淋巴细胞D_2减少。这表明，钙抑制NA诱导的产热BAT以及收缩外周血管。胰高血糖素的作用在Ca处理的大鼠和对照组之间没有差异。(2)食物摄入量的近交耐热，以及耐寒，FOK大鼠没有不同的标准：Wistar大鼠在这两个温暖的适应和寒冷的适应条件。(3)在冷习服FOK大鼠中，NA诱导的耗氧量增加大于对照品系。胰高血糖素诱导的Tcol增加在FOK大鼠中也更大。(4)急性冷暴露后，热习服和冷习服FOK大鼠血浆胰高血糖素水平均高于对照品系。(5)FOK大鼠BAT对胰高血糖素的EC_（max）D_（250）E_（max）D_（250）。(6)三磷酸肌醇（IP）D23、D2剂量依赖性地增加新生大鼠BAT的耗氧量。(7)催乳素（PRL）处理降低BAT对胰高血糖素的产热反应。(8)PCR分析显示BAT中存在PRL受体mRNA信号。短型PRL受体mRNA的信号强于长型PRL受体mRNA的信号，且新生BAT的短型PRL受体mRNA的信号强于成年BAT的短型PRL受体mRNA的信号。胰高血糖素刺激BAT产热活性的途径是IP β-D_（23）β-D_（2）-Ca ~（2+）β-D_（12）+Ca ~（2+）β-D_（1）途径，该途径受PRL抑制。

项目成果

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Suzuki, J. 等人：“冷适应 68 代的大鼠比目鱼肌中的毛细血管几何结构”同上。

Nakagaki,I.et al.: "Changes in intracellular electrolyte levels of brown adipocytes of cold acclimated rat." Cell Structure and Function. 23(Suppl.). 121 (1998)

Nakagaki,I.et al.：“冷适应大鼠棕色脂肪细胞内电解质水平的变化。”

Yahata, T. and Terayama, K.: "Roles of glucagon on nonshivering thermogesis and its control mechanism"Bulletin of Nayoro City College. 29. 15-21 (1997)

Yahata, T. 和 Terayama, K.：“胰高血糖素对非颤抖产热的作用及其控制机制”名寄城市学院通报。

Gao, M. et al.: "The capillary of subendocardium of left ventricle in rats reared at a low temperature for many generations"Acta Physiol. Scand.. 160. 67-70 (1997)

高，M.等：“低温饲养多代大鼠左心室心内膜下毛细血管”Acta Physiol。

八幡剛浩・寺山和幸: "非ふるえる熱産生に果たすグルカゴンの役割とその調節"市立名寄短期大学紀要. 29. 15-21 (1997)

Takehiro Yahata 和 Kazuyuki Terayama：“胰高血糖素在非颤抖产热中的作用及其调节”名寄市短期大学公告 29. 15-21 (1997)。