Circadian clock rhythms in different adipose tissue model systems
Circadian clock rhythms in different adipose tissue model systems
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DOI：
10.1080/07420528.2018.1494603
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发表时间：
2018-11-02
影响因子：
2.8
通讯作者：
Oster, Henrik
中科院分区：
文献类型：
--
作者：
Friedrichs, Maureen;Kolbe, Isa;Oster, Henrik
昼夜节律钟控制的脂肪组织24小时振荡在能量平衡的调节中起重要作用，因此代表了预防和治疗代谢性疾病的潜在药物靶点。对于药理学筛选，需要可扩展的脂肪模型系统，其在很大程度上概括了体内观察到的时钟特性。在这项研究中，我们比较了来自小鼠脂肪组织的不同离体和体外模型的分子生物钟调节。来自PER 2：：LUC昼夜节律报告小鼠的三个不同脂肪库的外植体培养物揭示了离体发光的稳定和可比较的节律。同样，这些小鼠的原代前和成熟脂肪细胞显示出稳定的发光节律，但在成熟脂肪细胞中具有强阻尼。在野生型前脂肪细胞的慢病毒转导后，使用Bmal 1-luc和Per 2-luc报告基因也观察到稳定的昼夜节律周期。鼠棕色、皮下和附睾脂肪组织来源的SV 40永生化脂肪细胞显示出核心时钟基因Bmal 1、Per 2、Dbp和REV-erb α在前成熟和成熟脂肪细胞中的节律性mRNA表达，总体mRNA水平和幅度与成熟相关增加。时钟基因mRNA节律相位的比较揭示了体内和离体条件之间的特定变化。总之，我们的数据表明，脂肪培养系统在很大程度上模仿体内组织时钟调节。因此，外植体和细胞系统可能是有用的工具，用于大规模筛选脂肪时钟调节因子。
Circadian clock-controlled 24-h oscillations in adipose tissues play an important role in the regulation of energy homeostasis, thus representing a potential drug target for prevention and therapy of metabolic diseases. For pharmacological screens, scalable adipose model systems are needed that largely recapitulate clock properties observed in vivo. In this study, we compared molecular circadian clock regulation in different ex vivo and in vitro models derived from murine adipose tissues. Explant cultures from three different adipose depots of PER2::LUC circadian reporter mice revealed stable and comparable rhythms of luminescence ex vivo. Likewise, primary pre- and mature adipocytes from these mice displayed stable luminescence rhythms, but with strong damping in mature adipocytes. Stable circadian periods were also observed using Bmal1-luc and Per2-luc reporters after lentiviral transduction of wild-type pre-adipocytes. SV40 immortalized adipocytes of murine brown, subcutaneous and epididymal adipose tissue origin showed rhythmic mRNA expression of the core clock genes Bmal1, Per2, Dbp and REV-erb alpha in pre- and mature adipocytes, with a maturation-associated increase in overall mRNA levels and amplitudes. A comparison of clock gene mRNA rhythm phases revealed specific changes between in vivo and ex vivo conditions. In summary, our data indicate that adipose culture systems to a large extent mimic in vivo tissue clock regulation. Thus, both explant and cell systems may be useful tools for large-scale screens for adipose clock regulating factors.