Characteristics of circadian gene expressions in mice white adipose tissue and 3T3-L1 adipocytes
Characteristics of circadian gene expressions in mice white adipose tissue and 3T3-L1 adipocytes
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DOI：
10.1248/jhs.51.21
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发表时间：
2005-02-01
影响因子：
--
通讯作者：
Tezuka, M
中科院分区：
文献类型：
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作者：
Aoyagi, T;Shimba, S;Tezuka, M
大多数(如果不是全部)生理和行为过程都表现出昼夜节律。最近，在一些外周组织中发现了类似于视交叉上核(SCN)神经元的分子时钟。在外周组织中，最近的一些研究发现白色脂肪组织分泌许多生物活性分子，如瘦素、抵抗素、脂联素等。重要的是，这些细胞因子样分子的水平与糖尿病、心血管疾病和肥胖等生活方式相关疾病的发生有关。在这项研究中，我们试图表征昼夜节律基因在脂肪组织中的表达。在这里，我们展示了几个时钟基因的表达在小鼠白色脂肪细胞中表现出每日的振荡。此外，还观察到脂肪细胞相关基因如过氧化体增殖物激活受体(PPAR)、Gamma2等的昼夜节律表达。有趣的是，一些时钟基因在脂肪细胞中的表达模式与在含有前脂肪细胞的间质血管部分中的表达模式不同。除了这些体内研究，我们还证明了血清或地塞米松休克诱导了培养的脂肪细胞时钟基因的循环表达。因此，我们得出结论，脂肪细胞含有与在SCN中发现的相似的昼夜节律所需的机制。然后我们研究了PPARGamma2配体的药理作用是否依赖于给药时间。与其受体水平一致，PPARGammarigand在小鼠体内的药理作用在黑暗时期比在光照时期更有效。这些结果提示，以脂肪细胞功能为靶点的计时疗法对改善高脂血症等相关疾病的症状是有效的。
Most, if not all, of physiological and behavioral processes exhibit circadian rhythms. Recently, molecular clocks similar to those operating in the suprachiasmatic nucleus (SCN) neurons have been found in several peripheral tissues. Among peripheral tissues, several recent studies have revealed that white adipose tissues secrete a number of biologically active molecules such as leptin, resistin, adiponectin, etc. Importantly, the levels of these cytokine-like molecules are associated with development of lifestyle-related diseases such as diabetic mellitus, cardiovascular diseases, and obesity. In this study, we attempted to characterize circadian gene expression in adipose tissue. Here, we show that the expression of several clock genes exhibits daily oscillation in mice white adipocytes. Circadian expression of adipocytes-related genes such as peroxisome proliferator-activated receptor (PPAR) gamma2 was also observed. Interestingly, expression pattern of some clock genes in adipocytes is distinct from that in stromal-vascular fractions containing preadipocytes. In addition to these in vivo studies, we demonstrated that serum- or dexamethasone-shock induced the cyclic gene expression of clock genes in cultured adipocytes. Consequently, we are led to conclude that adipocytes contain the machineries necessary for circadian oscillation similar to that found in SCN. We then examined that whether the pharmacological effects of PPARgamma2 ligand depend on the time of administration. Consist with its receptor levels, the pharmacological effects of PPARgammaligand administered during a dark period were more efficient than those during a light period in mice. These results suggest that chronotherapy targeted for adipocyte functions could be effective in improving of the symptoms of hyperlipidemia and other related diseases.