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用硫代葡萄糖金使小鼠肥胖后,其棕色脂肪组织对寒冷的反应减弱。

Attenuated response to cold of brown adipose tissue of mice made obese with gold thioglucose.

作者信息

Eley J, Himms-Hagen J

机构信息

Department of Biochemistry, University of Ottawa, Ont., Canada.

出版信息

Can J Physiol Pharmacol. 1989 Feb;67(2):116-21. doi: 10.1139/y89-020.

DOI:10.1139/y89-020
PMID:2496911
Abstract

In a first study, mice made obese with gold thioglucose became hypothermic when exposed to 4 degrees C. In a second study, lean mice and mice made obese with gold thioglucose (dynamic phase) were acclimated to 14 degrees C for up to 2 weeks and their brown adipose tissue was studied. The cold-induced increase in thyroxine 5'-deiodinase activity was initially slightly smaller in obese mice, but by 24 h and 2 weeks in the cold the activity of thyroxine 5'-deiodinase was the same in lean and obese mice. Unexpectedly, the elevated activity of 5'-deiodinase returned to the low level seen in warm-acclimated mice in both lean and obese mice after 2 weeks of cold acclimation. In gold thioglucose obese mice, a progressive cold-induced increase in the binding of guanosine diphosphate to isolated mitochondria, an index of both acute thermogenic activation and a long-term increase in uncoupling protein concentration, paralleled that seen in normal lean mice and remained at a high level after 2 weeks in the cold, although still remaining slightly lower than normal. It is not clear how a high level of mitochondrial GDP binding is maintained in cold-acclimated mice at the same time as a low level of thyroxine 5'-deiodinase activity when both are believed to be controlled by the sympathetic nervous system. We conclude that the gold thioglucose obese mouse can activate its brown adipose tissue fairly normally when it is exposed to cold, but that some attenuation of this process may contribute to the impaired survival of this mouse at low temperatures.

摘要

在第一项研究中,用硫代葡萄糖金诱导肥胖的小鼠在暴露于4摄氏度时体温降低。在第二项研究中,将瘦小鼠和用硫代葡萄糖金诱导肥胖的小鼠(动态期)在14摄氏度下适应长达2周,并对它们的棕色脂肪组织进行研究。肥胖小鼠中,寒冷诱导的甲状腺素5'-脱碘酶活性最初略有降低,但在寒冷环境中24小时及2周后,瘦小鼠和肥胖小鼠的甲状腺素5'-脱碘酶活性相同。出乎意料的是,在寒冷适应2周后,瘦小鼠和肥胖小鼠中5'-脱碘酶升高的活性均恢复到温暖适应小鼠中的低水平。在硫代葡萄糖金诱导肥胖的小鼠中,寒冷诱导的鸟苷二磷酸与分离的线粒体结合逐渐增加,这是急性产热激活和解偶联蛋白浓度长期增加的指标,与正常瘦小鼠相似,并且在寒冷环境中2周后仍保持在高水平,尽管仍略低于正常水平。目前尚不清楚在寒冷适应的小鼠中,当两者都被认为受交感神经系统控制时,甲状腺素5'-脱碘酶活性处于低水平的同时,线粒体GDP结合如何维持在高水平。我们得出结论,硫代葡萄糖金诱导肥胖的小鼠在暴露于寒冷时能够相当正常地激活其棕色脂肪组织,但这一过程的某些减弱可能导致该小鼠在低温下存活率受损。

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