Expression of the uncoupling protein 1 from the aP2 gene promoter stimulates mitochondrial biogenesis in unilocular adipocytes in vivo
Expression of the uncoupling protein 1 from the aP2 gene promoter stimulates mitochondrial biogenesis in unilocular adipocytes in vivo
复制标题
DOI：
10.1046/j.0014-2956.2002.02627.x
复制
发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Kopecky, J
中科院分区：
文献类型：
--
作者：
Rossmeisl, M;Barbatelli, G;Kopecky, J
线粒体解偶联蛋白1 （UCP1）是多室棕色脂肪细胞的特异性标志物。aP2-Ucp1小鼠白色脂肪中的异位UCP1通过增加能量消耗和减少原位脂肪生成两种方式减轻肥胖的发展。为了进一步分析呼吸解偶联对白色脂肪的影响，我们研究了异位UCP1对脂肪细胞形态和线粒体生物发生的影响。在aP2-Ucp1和幼龄对照（5周龄）小鼠的皮下白色脂肪中，发现了大量的多室脂肪细胞，而在成年（7- 9月龄）小鼠中没有多室脂肪细胞。两种基因型的附睾脂肪中均存在单眼细胞。在aP2-Ucp1小鼠的两个脂肪库中，随着年龄的增长，UCP1转录物和UCP1抗原的水平下降，皮下脂肪中的UCP1转录物和抗原水平高于附睾脂肪。在任何情况下，异位UCP1都不能诱导单房脂肪细胞向多房脂肪细胞转化。单眼脂肪细胞中异位UCP1的存在与UCP2和线粒体细胞色素氧化酶（COX IV）亚基IV转录本的升高以及线粒体细胞色素含量的增加有关。电镜显示单眼脂肪细胞内UCP1异位导致线粒体形态改变，线粒体含量增加。在3T3-L1脂肪细胞中，2,4-二硝基苯酚增加了COX IV和核呼吸因子-1转录本的水平。我们的研究结果表明，白色脂肪单眼脂肪细胞的呼吸解偶联既能诱导线粒体生物发生，又能减少肥胖的发生。
Mitochondrial uncoupling protein 1 (UCP1) is a specific marker of multilocular brown adipocytes. Ectopic UCP1 in white fat of aP2-Ucp1 mice mitigates development of obesity by both, increasing energy expenditure and decreasing in situ lipogenesis. In order to further analyse consequences of respiratory uncoupling in white fat, the effects or the ectopic UCP1 on the morphology of adipocytes and biogenesis of mitochondria in these cells were studied. In subcutaneous white fat of both aP2-Ucp1 and young control (5-week-old) mice, numerous multilocular adipocytes were found, while they were absent in adult (7- to 9-month-old) animals. Only unilocular cells were present in epididymal fat of both genotypes. In both fat depots of aP2-Ucp1 mice, the levels of the UCP1 transcript and UCP1 antigen declined during ageing, and they were higher in subcutaneous than in epididymal fat. Under no circumstances could ectopic UCP1 induce the conversion of unilocular into multilocular adipocytes. Presence of ectopic UCP1 in unilocular adipocytes was associated with the elevation of the transcripts for UCP2 and for subunit IV of mitochondrial cytochrome oxidase (COX IV), and increased content of mitochondrial cytochromes. Electron microscopy indicated changes of mitochondrial morphology and increased mitochondrial content due to ectopic UCP1 in unilocular adipocytes. In 3T3-L1 adipocytes, 2,4-dinitrophenol increased the levels of the transcripts for both COX IV and for nuclear respiratory factor-1. Our results indicate that respiratory uncoupling in unilocular adipocytes of white fat is capable of both inducing mitochondrial biogenesis and reducing development of obesity.