Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides.

Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides.
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DOI:
10.1016/j.cmet.2013.12.016
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发表时间:
2014-02-04
期刊:
影响因子:
29
通讯作者:
Asher G
Asher G
中科院分区:
生物学1区
文献类型:
--
作者:
Adamovich Y;Rousso-Noori L;Zwighaft Z;Neufeld-Cohen A;Golik M;Kraut-Cohen J;Wang M;Han X;Asher G

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生物钟在协调日常生理过程中起着重要作用,其紊乱会引发诸如脂肪肝和肥胖等代谢性疾病。为了研究生物钟在脂质稳态中的作用,我们对野生型和生物钟紊乱的小鼠的肝脏组织进行了广泛的脂质组学分析,这些小鼠要么自由进食,要么夜间进食。令我们惊讶的是,在两种小鼠品系中,相似比例(约17%)的脂质都存在波动,其中最显著的是甘油三酯,但波动的相位完全不同。此外,一些主要的脂质调节因子(例如PPARα)以及参与甘油三酯代谢的酶在生物钟紊乱的小鼠中仍保留其生物钟节律性表达。夜间限时进食改变了甘油三酯积累的相位,并使野生型小鼠肝脏中的甘油三酯水平降低了约50%。我们的研究结果表明,生物钟和进食时间决定了肝脏中甘油三酯积累的相位和水平,然而在生物钟功能缺失的情况下,甘油三酯的波动仍可存在。
Circadian clocks play a major role in orchestrating daily physiology, and their disruption can evoke metabolic diseases such as fatty liver and obesity. To study the role of circadian clocks in lipid homeostasis, we performed an extensive lipidomic analysis of liver tissues from wild type and clock-disrupted mice, fed either ad libitum or night fed. To our surprise, a similar fraction of lipids (~17%) oscillated in both mouse strains, most notably triglycerides, but with completely different phases. Moreover, several master lipid regulators (e.g. PPARα) and enzymes involved in triglyceride metabolism retained their circadian expression in clock-disrupted mice. Nighttime restricted feeding shifted the phase of triglyceride accumulation and resulted in ~50% decrease in hepatic triglyceride levels in wild type mice. Our findings suggest that circadian clocks and feeding time dictate the phase and levels of hepatic triglyceride accumulation, however oscillations in triglycerides can persist in the absence of a functional clock.
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