Time-Restricted Feeding Alters the Innate Immune Response to Bacterial Endotoxin.

Time-Restricted Feeding Alters the Innate Immune Response to Bacterial Endotoxin.
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DOI:
10.4049/jimmunol.1701136
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发表时间:
2018-01-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Nelson RJ
Nelson RJ
中科院分区:
其他
文献类型:
--
作者:
Cissé YM;Borniger JC;Lemanski E;Walker WH 2nd;Nelson RJ

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内源性生物钟的一个重要的信号,独立于光,是食物摄入。昼夜节律和免疫系统是相互关联的;通过夜间光照或核心时钟组件的基因消融来强制破坏昼夜节律钟会损害免疫功能。食物摄入的时间会影响生物钟的各个方面,但其对免疫功能的影响尚不清楚。我们检验了食物摄入的时间限制改变先天免疫反应的假设。成年雄性Swiss韦伯斯特小鼠在夜间、白天或随意进食4周,然后在活动期(ZT 12:实验1)或非活动期(ZT 0:实验2)开始前给予脂多糖(LPS)。LPS给药后3小时,收集血液,并测试血清对大肠杆菌的细菌杀伤能力,作为免疫功能的功能测定。此外,还检测了血清(蛋白质)、脾脏和下丘脑(mRNA)中的细胞因子表达。白天喂养的小鼠在活动期抑制细菌杀伤能力和血清细胞因子对LPS的反应(ZT 12)。夜间喂养的小鼠增加杀菌能力,以及血清和下丘脑的某些促炎细胞因子的mRNA反应在活跃期。当LPS攻击发生在非活动期(ZT 0)时,只有白天喂养的小鼠增强血清细胞因子应答,这并不导致杀菌能力增强。这些数据表明,不定时喂养与免疫功能具有功能相关性,并为昼夜节律,代谢和免疫系统的整合提供了进一步的证据。
An important entraining signal for the endogenous circadian clock, independent of light, is food intake. The circadian and immune systems are linked; forced desynchrony of the circadian clock via nighttime light exposure or genetic ablation of core clock components impairs immune function. The timing of food intake affects various aspects of the circadian clock, but its effects on immune function are unknown. We tested the hypothesis that temporal desynchrony of food intake alters innate immune responses. Adult male Swiss Webster mice were provided with food either during the night, the day, or ad libitum for four weeks, followed by administration of lipopolysaccharide (LPS) either prior to the onset of the active (ZT12: Experiment 1) or inactive (ZT0: Experiment 2) phase. Three hours after LPS administration, blood was collected and serum was tested for bacteria killing capacity against Escherichia coli, as a functional assay of immune function. Additionally, cytokine expression was examined in the serum (protein), spleen, and hypothalamus (mRNA). Day-fed mice suppressed bacteria killing capacity and serum cytokine responses to LPS during the active phase (ZT12). Night-fed mice increased bactericidal capacity, as well as serum and hypothalamic mRNA responses of certain pro-inflammatory cytokines during the active phase. Only Day-fed mice enhanced serum cytokine responses when LPS challenge occurred during the inactive phase (ZT0), this did not result in enhanced bactericidal capacity. These data suggest that mistimed feeding has functional relevance for immune function, and provides further evidence for the integration of the circadian, metabolic, and immune systems.
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