Regular Feeding Plays an Important Role in Cholesterol Homeostasis Through the Liver Circadian Clock
Regular Feeding Plays an Important Role in Cholesterol Homeostasis Through the Liver Circadian Clock
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DOI：
10.1161/circresaha.109.199034
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发表时间：
2009-09
影响因子：
20.1
通讯作者：
Daisuke Yamajuku;Shingo Okubo;Tomonori Haruma;Takahiko Inagaki;Yuji Okuda;T. Kojima;Keiji Noutomi;S. Hashimoto;H. Oda
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文献类型：
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作者：
Daisuke Yamajuku;Shingo Okubo;Tomonori Haruma;Takahiko Inagaki;Yuji Okuda;T. Kojima;Keiji Noutomi;S. Hashimoto;H. Oda
原理：外周时钟控制以及昼夜节律与生理和疾病的相关性是哺乳动物昼夜生物学的主要问题。目的：研究肝钟的生理功能。方法和结果：我们建立了一种抑制喂养计划的方案，构成了每6小时提供一次的高胆固醇饮食，而不改变能量和胆固醇的摄入量。我们发现，暴露在这种疗法下的大鼠出现了高胆固醇血症。在肝脏中，几个时钟基因的表达节律性被打乱。此外，编码胆固醇转化为胆汁酸的限速酶的CYP7A1基因在夜间的表达也转变为白天的模式。事实上，抑制正常的进食节律增加了肝脏极低密度脂蛋白胆固醇的分泌速度，并减少了粪便胆汁酸的排泄。结论：我们的结果表明，不仅食物的数量和质量，而且用餐的时间也对健康有至关重要的影响。
Rationale: Peripheral clock control and the relevance of the circadian rhythm to physiology and disease are major questions in mammalian circadian biology. Objective: We examined the physiological functions of the liver clock. Methods and Results: We established a suppressed feeding schedule regimen constituting a high-cholesterol diet delivered every 6 hours without changes in energy and cholesterol intake. We found that rats exposed to this regimen developed hypercholesteremia. In the liver, the rhythmicity of expression of several clock genes was disrupted. Furthermore, the nocturnal expression of the CYP7A1 gene, which encodes the rate-limiting enzyme for the conversion of cholesterol to bile acids, was shifted to a diurnal pattern. Indeed, suppression of a regular feeding rhythm increased the secretion rate of very-low-density lipoprotein cholesterol from the liver and decreased the excretion of fecal bile acids. Conclusions: Our results demonstrated that not only the amount and quality of food but also the timing of meals has crucial health implications.