Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by −3.7 hours and −4.2 hours, respectively, compared to −6.6 hours and −4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.

中文翻译：

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临床代谢生物标志物的内源性昼夜节律调节和相位重置


轮班工作和昼夜节律紊乱与不良代谢影响有关。因此，我们使用 40 小时恒定常规方案（CR；恒定环境和行为条件）检查代谢健康的临床生物标志物是否处于内源性昼夜节律调节之下，并评估了定期睡眠和进餐的典型日常条件的影响（基线；8 小时睡眠）晚上，16 小时清醒期间的四餐），以了解这些节律的相位和幅度。此外，我们还测试了这些昼夜节律是否在模拟轮班期间重置。在 CR（n = 16 名男性，平均年龄 ± SD = 23.4 ± 2.3 岁）下，我们发现胆固醇、HDL 和 LDL、白蛋白和总蛋白、VLDL 和甘油三酯存在内源性昼夜节律。除胆固醇外，其他节律在基线条件下均被掩盖，胆固醇在两种条件下具有几乎相同的相位。然后，在一项模拟轮班研究（n = 25，14 名女性，36.3 ± 8.9 岁）中，通过四个方案测试了胆固醇节律的重置和暗光褪黑激素发作 (DLMO)；两个突然延迟 8 小时并暴露在富含蓝光或标准白光下；突然或逐渐提前 8 小时（5 天内每天 1.6 小时），两者都暴露在富含蓝色的白光下。在延迟方案中，胆固醇节律分别晚了-3.7小时和-4.2小时，而DLMO的则为-6.6小时和-4.7小时。与 DLMO 中的+3.1 小时和+2.8 小时相比，在突然（+5.1 小时）方案中胆固醇水平显着升高，但在渐进（+2.1 小时）方案中则没有显着升高。探索性小组分析比较了两项研究中所有代谢生物标志物的相位，显示了由于模拟轮班工作而出现相移的证据。 这些结果表明，代谢健康的临床生物标志物处于内源性昼夜节律调节之下，但这些节律的表达很大程度上受到环境因素的影响。这些节律也可以重置，这对于理解轮班工作导致的行为变化和昼夜节律变化如何扰乱代谢功能具有重要意义。