Characterization of peripheral circadian clocks in adipose tissues
Characterization of peripheral circadian clocks in adipose tissues
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DOI：
10.2337/diabetes.55.04.06.db05-0873
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发表时间：
2006-04-01
期刊：
影响因子：
7.7
通讯作者：
Gimble, JM
中科院分区：
文献类型：
--
作者：
Zvonic, S;Ptitsyn, AA;Gimble, JM
首先在视交叉上核中描述，生物钟已经在几个外周组织中发现。尽管肥胖与瘦素、脂联素和其他脂肪源性细胞因子的昼夜节律表达谱失调有关，但目前还没有对脂肪库中的昼夜节律钟机制进行全面分析。在这项研究中，我们显示了昼夜节律振荡基因（Npas 2，Bmal 1，Perl-3和Cry 1 -2）和时钟控制的下游基因（Rev-erb alpha，Rev-erb beta，Dbp，E4 bp 4，Stra 13和Id 2）在小鼠棕色，腹股沟和附睾（BAT，iWAT和eWAT）脂肪组织中的稳健和协调表达。这些结果与肝脏中相应的基因表达和昼夜节律功能的血清标志物相关。通过Affyssin微阵列分析，我们确定了BAT，iWAT和肝脏中共有昼夜表达谱的650个基因。此外，我们已经证明，时间限制喂养导致协调相移的昼夜节律的主要振荡基因和它们的下游目标在脂肪组织中的表达。昼夜节律振荡基因在脂肪中的存在具有显著的代谢意义，并且它们的表征可能对于疾病（诸如肥胖、2型糖尿病和代谢综合征）的发病机制和治疗具有潜在的治疗相关性。
First described in the suprachiasmatic nucleus, circadian clocks have since been found in several peripheral tissues. Although obesity has been associated with dysregulated circadian expression profiles of leptin, adiponectin, and other fat-derived cytokines, there have been no comprehensive analyses of the circadian clock machinery in adipose depots. In this study, we show robust and coordinated expression of circadian oscillator genes (Npas2, Bmal1, Perl-3, and Cry1-2) and clock-controlled downstream genes (Rev-erb alpha, Rev-erb beta, Dbp, E4bp4, Stra13, and Id2) in murine brown, inguinal, and epididymal (BAT, iWAT, and eWAT) adipose tissues. These results correlated with respective gene expression in liver and the serum markers of circadian function. Through Affymetrix microarray analysis, we identified 650 genes that shared circadian expression profiles in BAT, iWAT, and liver. Furthermore, we have demonstrated that temporally restricted feeding causes a coordinated phase-shift in circadian expression of the major oscillator genes and their downstream targets in adipose tissues. The presence of circadian oscillator genes in fat has significant metabolic implications, and their characterization may have potential therapeutic relevance with respect to the pathogenesis and treatment of diseases such as obesity, type 2 diabetes, and the metabolic syndrome.