Time-of-Day Effects on Metabolic and Clock-Related Adjustments to Cold.

Time-of-Day Effects on Metabolic and Clock-Related Adjustments to Cold.
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DOI:
10.3389/fendo.2018.00199
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发表时间:
2018
影响因子:
5.2
通讯作者:
Kalsbeek A
Kalsbeek A
中科院分区:
医学2区
文献类型:
--
作者:
Machado FSM;Zhang Z;Su Y;de Goede P;Jansen R;Foppen E;Coimbra CC;Kalsbeek A

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环境条件的每日周期性变化是包括哺乳动物在内的大多数生物物种进行预期和适应性调整的关键信号。较低的环境温度刺激棕色脂肪组织(BAT)和骨骼肌的产热活动。鉴于内源性生物钟的分子组成部分与直接参与体温防御的热和代谢机制相互作用,本研究评估了在光/暗周期的不同时间窗口对冷刺激的差异稳态反应。雄性Wistar大鼠在Zeitgeber时间3、7、11、15、19和23开始的6个时间点之一经受3小时冷环境温度(4°C)的单次发作。在控制和寒冷条件下,在每个时间点记录代谢率、核心体温、自发活动(LA)、进食和饮水行为。刺激后立即对大鼠实施安乐死,并收集比目鱼肌和BAT用于实时PCR。在轻阶段(即,非活动期),冷暴露导致轻微的体温过高(p < 0.001)。光相冷暴露也增加代谢率和LA(p < 0.001)。此外,在非活动期,脂肪氧化代谢的发生率降低(p < 0.001)。这些代谢变化伴随着核心时钟基因表达的时间和组织特异性变化,如DBP(p < 0.0001)和REV-ERBα(p < 0.01),比目鱼肌骨骼肌中的PER 2(p <0.05)、ERB 1(p <0.05)、ERB 2(p < 0.01)和REV-ERBα(p < 0.05)。此外,参与底物氧化和产热的基因受到影响,在一天中的时间和组织特异性的方式冷暴露。在冷暴露期间底物动员和氧化的日时调节提供了生理和代谢反应的昼夜调节的明确示例。有趣的是,冷暴露后,一天中的时间主要影响比目鱼肌中的生物钟基因表达,尽管在光暗周期中LA的变化相当。目前的研究结果进一步证明了内部时钟在不同外周器官(如骨骼肌和BAT)中的组织特异性作用。
Daily cyclic changes in environmental conditions are key signals for anticipatory and adaptive adjustments of most living species, including mammals. Lower ambient temperature stimulates the thermogenic activity of brown adipose tissue (BAT) and skeletal muscle. Given that the molecular components of the endogenous biological clock interact with thermal and metabolic mechanisms directly involved in the defense of body temperature, the present study evaluated the differential homeostatic responses to a cold stimulus at distinct time-windows of the light/dark-cycle. Male Wistar rats were subjected to a single episode of 3 h cold ambient temperature (4°C) at one of 6 time-points starting at Zeitgeber Times 3, 7, 11, 15, 19, and 23. Metabolic rate, core body temperature, locomotor activity (LA), feeding, and drinking behaviors were recorded during control and cold conditions at each time-point. Immediately after the stimulus, rats were euthanized and both the soleus and BAT were collected for real-time PCR. During the light phase (i.e., inactive phase), cold exposure resulted in a slight hyperthermia (p < 0.001). Light phase cold exposure also increased metabolic rate and LA (p < 0.001). In addition, the prevalence of fat oxidative metabolism was attenuated during the inactive phase (p < 0.001). These metabolic changes were accompanied by time-of-day and tissue-specific changes in core clock gene expression, such as DBP (p < 0.0001) and REV-ERBα (p < 0.01) in the BAT and CLOCK (p < 0.05), PER2 (p < 0.05), CRY1 (p < 0.05), CRY2 (p < 0.01), and REV-ERBα (p < 0.05) in the soleus skeletal muscle. Moreover, genes involved in substrate oxidation and thermogenesis were affected in a time-of-day and tissue-specific manner by cold exposure. The time-of-day modulation of substrate mobilization and oxidation during cold exposure provides a clear example of the circadian modulation of physiological and metabolic responses. Interestingly, after cold exposure, time-of-day mostly affected circadian clock gene expression in the soleus muscle, despite comparable changes in LA over the light–dark-cycle. The current findings add further evidence for tissue-specific actions of the internal clock in different peripheral organs such as skeletal muscle and BAT.
DOI: 10.1038/nature12642
发表时间: 2013-11-21
期刊: Nature
影响因子: 64.8
作者:
Gerhart-Hines Z;Feng D;Emmett MJ;Everett LJ;Loro E;Briggs ER;Bugge A;Hou C;Ferrara C;Seale P;Pryma DA;Khurana TS;Lazar MA
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发表时间: 1978-01-01
影响因子: 5.5
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