Uqcrc1基因在白色脂肪分化成熟和棕样化过程中的作用
发布时间：2018-08-18 17:46
【摘要】：近年来,随着人们认识到脂肪细胞与肥胖及相关疾病息息相关,人们对脂肪细胞的研究的兴趣迎来飞跃性的增长,特别是在过去几年,科研工作者发现了除白色脂肪细胞和棕色脂肪细胞之外的第三种脂肪细胞,即米色脂肪细胞,对脂肪细胞发育和分裂分化过程有了更加深入的认识。肥胖与脂肪细胞的甘油三酯累积密切相关,研究发现,白色脂肪细胞(主要功能是储存脂肪)在特定作用下分化为具有产热作用且消耗自身甘油三酯的米色脂肪细胞,这种转化途径引起了广泛关注。白色脂肪细胞转化为米色脂肪细胞是由多因子调控的,研究白色脂肪细胞或者前脂肪细胞分化为米色脂肪细胞的关键调控基因,发现分化过程中的重要转录因子,将为肥胖疾病和相关代谢疾病的治疗提供重要的理论依据。泛醌细胞色素 c 还原酶 1 基因(Ubiquinol-cytochrome c reductase core protein 1,Uqcrc1),编码线粒体呼吸作用复合体Ⅲ(呼吸链的重要组成部分)的一个亚基。线粒体在棕色脂肪细胞和米色脂肪细胞产热过程中起着关键作用。因此,本文以经典的体外细胞模型--前体脂肪细胞系3T3-L1作为研究载体,利用慢病毒介导的RNA干扰(RNA interference,RNAi)技术抑制前脂肪细胞3T3-L1的Uqcrc1基因,并利用广泛使用的鸡尾酒法(地塞米松、胰岛素和3-异丁基-1-甲基黄嘌呤)诱导前体脂肪细胞3T3-L1分化为白色脂肪细胞,并利用药物组合(胰岛素,3-异丁基-1-甲基黄嘌呤,罗格利酮,异丙肾上腺素)将白色脂肪转化为米色脂肪细胞,来研究3T3-L1分化为米色脂肪细胞的潜能及Uqcrc1基因在脂肪细胞分化过程中的作用。实验结果显示,与对照组相比较,经携带干扰序列的慢病毒感染的3T3-L1细胞的基因Uqcrc1表达量大约降低了 90%。通过对比分化成熟的3T3-L1细胞中脂肪标记基因Fabp4表达量的差异以及油红染色结果,笔者发现,抑制了3T3-L1的Uqcrc1基因后,细胞分化效率降低,脂滴积累减少,分化潜能被抑制。诱导3T3-L1形成米色脂肪细胞的实验中,细胞中关键产热基因Ucp1(解偶联蛋白),关键转录控制因子基因C/EBPβ Prdm16,Pgc-1 以及米色脂肪细胞标记基因Cd137,Cited1,Tmem26,Tbx1表达量均有显著性升高;利用慢病毒系统抑制3T3-L1细胞中Uqcrc1基因后,以上基因均显著性低于对照组。因此,抑制Uqcrc1基因表达在一定程度上抑制了白色脂肪细胞分化及其棕样化。根据以上结果,Uqcrc1基因在白色脂肪生成以及白色脂肪细胞棕样化扮演的重要角色,为肥胖治疗及其潜能提供了依据。
[Abstract]:In recent years, with the realization that adipocytes are closely related to obesity and related diseases, interest in adipocyte research has grown dramatically, especially in the past few years. Researchers have discovered that the third kind of adipocytes, beige adipocytes, besides white adipocytes and brown adipocytes, have a deeper understanding of adipocyte development and differentiation. Obesity is closely related to the accumulation of triglycerides in adipocytes. Studies have found that white fat cells (the main function of which is to store fat) differentiate into beige fat cells that produce heat and consume their own triglycerides. This way of transformation has aroused widespread concern. The transformation of white adipocytes into beige adipocytes is regulated by multiple factors. The key regulatory genes for the differentiation of white adipocytes or preadipocytes into beige adipocytes were studied, and the important transcription factors in the process of differentiation were found. It will provide important theoretical basis for the treatment of obesity and related metabolic diseases. Ubiquinone cytochrome c reductase 1 (Ubiquinol-cytochrome c reductase core protein 1) is a subunit encoding mitochondrial respiratory complex 鈪，
本文编号：2190217
[Abstract]:In recent years, with the realization that adipocytes are closely related to obesity and related diseases, interest in adipocyte research has grown dramatically, especially in the past few years. Researchers have discovered that the third kind of adipocytes, beige adipocytes, besides white adipocytes and brown adipocytes, have a deeper understanding of adipocyte development and differentiation. Obesity is closely related to the accumulation of triglycerides in adipocytes. Studies have found that white fat cells (the main function of which is to store fat) differentiate into beige fat cells that produce heat and consume their own triglycerides. This way of transformation has aroused widespread concern. The transformation of white adipocytes into beige adipocytes is regulated by multiple factors. The key regulatory genes for the differentiation of white adipocytes or preadipocytes into beige adipocytes were studied, and the important transcription factors in the process of differentiation were found. It will provide important theoretical basis for the treatment of obesity and related metabolic diseases. Ubiquinone cytochrome c reductase 1 (Ubiquinol-cytochrome c reductase core protein 1) is a subunit encoding mitochondrial respiratory complex 鈪，
本文编号：2190217
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