Department of Psychological and Brain Sciences, University of Massachusetts Amherst, Amherst, MA 01003, USA; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164, USA.
Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164, USA.
Brain Behav Immun. 2020 Aug;88:220-229. doi: 10.1016/j.bbi.2020.05.033. Epub 2020 May 12.
Metabolism and inflammation are linked at many levels. Sickness behaviors are elicited by the immune system's response to antigenic stimuli, and include changes in feeding and metabolism. The immune system is also regulated by the circadian (daily) clock, which generates endogenous rhythms, and synchronizes these rhythms to the light-dark cycle. Modern society has resulted in chronic misalignment or desynchronization of the circadian clock and the external environment. We have demonstrated that circadian desynchronization (CD) in mice alters metabolic function, and also affects both peripheral and central immune responses following a low-dose lipopolysaccharide (LPS) challenge. However, it is unclear how this altered immune response impacts sickness behaviors and metabolism following challenge. To test this, we housed male mice in circadian desynchronized (10-hours light:10-hours dark) or control (12-hours light:12-hours dark) conditions for 5-6 weeks. We then challenged mice with LPS (i.p., 0.4 mg/kg) or PBS and measured changes in body mass, feeding, drinking and locomotion using a comprehensive phenotyping system. Plasma, liver, and brain were collected 36 h post-inoculation (hpi) and inflammatory messengers were measured via multiplex cytokine/chemokine array and qPCR. We find that recovery of locomotion and body mass is prolonged in CD mice following LPS challenge. Additionally, at 36 hpi the expression of several proinflammatory cytokines differ depending on pre-inoculation lighting conditions. Our findings add to the growing literature which documents how desynchronization of circadian rhythms can lead to disrupted immune responses and changes in metabolic function.
代谢和炎症在多个层面上相互关联。疾病行为是由免疫系统对抗原刺激的反应引起的，包括摄食和代谢的变化。免疫系统也受昼夜节律（日常）钟的调节，昼夜节律钟产生内源性节律，并将这些节律与明暗周期同步。现代社会导致昼夜节律钟与外部环境的慢性失准或不同步。我们已经证明，小鼠的昼夜节律失调（CD）会改变代谢功能，并且在低剂量脂多糖（LPS）挑战后也会影响外周和中枢免疫反应。然而，尚不清楚这种改变的免疫反应如何影响挑战后的疾病行为和代谢。为了检验这一点，我们将雄性小鼠置于昼夜节律失调（10 小时光照：10 小时黑暗）或对照（12 小时光照：12 小时黑暗）条件下 5-6 周。然后，我们用 LPS（腹腔内，0.4mg/kg）或 PBS 挑战小鼠，并使用综合表型系统测量体重、摄食、饮水和运动的变化。在接种后 36 小时（hpi）收集血浆、肝脏和大脑，并通过多重细胞因子/趋化因子阵列和 qPCR 测量炎症信使。我们发现，在 LPS 挑战后，CD 小鼠的运动和体重恢复时间延长。此外，在 36 hpi 时，几种前炎症细胞因子的表达因接种前光照条件而异。我们的发现增加了越来越多的文献记录，即昼夜节律钟的失准如何导致免疫反应紊乱和代谢功能改变。
