[Regulatory mechanism of non-shivering thermogenesis in cold acclimation--with special reference to in vitro thermogenic activity and lipolysis of brown adipose tissue].

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.