Kikuchi K
First Department of Physiology, Asahikawa Medical College, Japan.
Hokkaido Igaku Zasshi. 1994 Sep;69(5):1102-14.
In vitro brown adipose tissue (BAT) thermogenesis from cold-acclimated (CA) rats has been shown to exhibit the decreased responses to noradrenaline (NA) and glucagon (G), although an enhanced biochemical machinery for thermogenesis develops in the tissue. The present study was undertaken to clarify the inhibitory mechanism of in vitro thermogenic responses of BAT in CA rats. NA-treated rats were injected NA (40 micrograms/100g BW) twice a day for 2 or 4 weeks. The other rats were kept at 25 +/- 1 degree C (warm controls: WC), 5 +/- 1 degree C (CA), or 5 +/- 1 degree C/6h/day (intermittent cold exposure: ICE) for 5-6 weeks. The oxygen consumption, and glycerol as well as free fatty acids (FFA) release were measured on finely minced tissue blocks in Krebs-Ringer phosphate buffer at 37 degrees C. In vitro BAT thermogenic responses to NA and G in NA-treated rats did not differ from those in vehicle-injected controls. NA as well as G increased-oxygen consumption was greatest in WC, followed by ICE and CA. NA as well as G increased glycerol and FFA releases in WC and ICE, but the degree of increment was greater in WC than that in ICE, while NA or G did not increase glycerol and FFA releases in CA. FFA/glycerol ratio in WC was decreased by NA as well as G, but it was not changed in ICE, and increased in CA. Mitochondrial GDP binding as an index of BAT thermogenic capacity did not differ between CA and WC under resting state (CA rats were transferred in warm condition before 18h at the beginning of the experiment), but it was significantly greater in ICE. GDP binding was significantly greater in CA sacrificed at 5 degrees C compared with WC and CA resting. Acute cold exposure (5 degrees C/1h) enhanced GDP binding in WC, resting CA and ICE resting, but the degree of increment was greater in CA and ICE than in WC. These findings suggest that cold exposure inhibits BAT thermogenic responses according to the duration NA action during cold exposure, by means of suppressing fatty acid utilization and/or masking uncoupling protein.
冷适应（CA）大鼠的体外棕色脂肪组织（BAT）产热已被证明对去甲肾上腺素（NA）和胰高血糖素（G）的反应减弱，尽管该组织中用于产热的生化机制有所增强。本研究旨在阐明CA大鼠BAT体外产热反应的抑制机制。用NA处理的大鼠每天注射两次NA（40微克/100克体重），持续2或4周。其他大鼠分别在25±1℃（温暖对照组：WC）、5±1℃（CA）或5±1℃/每天6小时（间歇性冷暴露：ICE）环境中饲养5 - 6周。在37℃的 Krebs - Ringer磷酸盐缓冲液中，对精细切碎的组织块测量其耗氧量、甘油以及游离脂肪酸（FFA）释放量。用NA处理的大鼠的BAT体外对NA和G的产热反应与注射溶剂的对照组无差异。NA和G增加的耗氧量在WC组最大，其次是ICE组和CA组。NA和G增加了WC组和ICE组的甘油和FFA释放，但WC组的增加程度大于ICE组，而NA或G在CA组未增加甘油和FFA释放。WC组中，NA和G降低了FFA/甘油比值，但ICE组未改变，CA组升高。作为BAT产热能力指标的线粒体GDP结合在静息状态下（实验开始前18小时将CA大鼠转移至温暖环境）CA组和WC组之间无差异，但ICE组显著更高。与WC组和静息CA组相比，在5℃处死的CA组的GDP结合显著更高。急性冷暴露（5℃/1小时）增强了WC组、静息CA组和静息ICE组的GDP结合，但CA组和ICE组的增加程度大于WC组。这些发现表明，冷暴露通过抑制脂肪酸利用和/或掩盖解偶联蛋白，根据冷暴露期间NA作用的持续时间来抑制BAT产热反应。
