Attenuating effect of Clock mutation on triglyceride contents in the ICR mouse liver under a high-fat diet
Attenuating effect of Clock mutation on triglyceride contents in the ICR mouse liver under a high-fat diet
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DOI：
10.1177/0748730407302625
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发表时间：
2007-08-01
影响因子：
3.5
通讯作者：
Shibata, Shigenobu
中科院分区：
文献类型：
--
作者：
Kudo, Takashi;Tarnagawa, Toru;Shibata, Shigenobu
能量稳态受昼夜节律控制，同步能量摄入和消耗。转录因子CLOCK是分子生物钟的关键组成部分，控制着许多种节律，如运动活动、体温和代谢功能。本研究的目的是利用Clock突变小鼠了解Clock基因在肝脏脂质代谢中的功能。具有ICR背景的时钟突变小鼠饲喂高脂肪饮食13周，检测肝脏甘油三酯、血清甘油三酯和血清游离脂肪酸水平。与野生型小鼠相比，高脂肪饮食的时钟突变小鼠肝脏中甘油三酯含量的增加明显较少。野生型小鼠肝脏中Acsl4和Fabp1的mRNA水平显示出每日节律，相比之下，clock突变小鼠在正常和高脂肪饮食条件下肝脏中Acs14和Fabp1基因表达的每日节律与野生型小鼠相比有所减弱。在clock突变小鼠中，与野生型小鼠相比，高脂肪饮食条件下肝脏中Acs14和Fabp1 mRNA的抑制可能减轻了肝脏中甘油三酯的积累。总之，作者证明，与喂食相同饮食的野生型小鼠相比，喂食高脂肪饮食时，具有Clock突变的小鼠通过抑制Acs14和Fabp1基因表达，肝脏中甘油三酯积累较少。
Energy homeostasis is subjected to a circadian control that synchronizes energy intake and expenditure. The transcription factor CLOCK, a key component of the molecular circadian clock, controls many kinds of rhythms, such as those for locomotor activity, body temperature, and metabolic functions. The purpose of the present study is to understand the function of the Clock gene during lipid metabolism in the liver using Clock-mutant mice. Clock-mutant mice with an ICR background were fed a high-fat diet for 13 weeks, and liver triglyceride, serum triglyceride, and serum free fatty acid levels were examined. Triglyceride content in the liver was significantly less increased in Clock-mutant mice on a high-fat diet compared to wild-type mice on a high-fat diet. Acsl4 and Fabp1 mRNA levels in the liver showed daily rhythms in wild-type mice, In contrast, Clock-mutant mice had attenuated daily rhythms of Acs14 and Fabp1 gene expression in the liver under both normal and high-fat diet conditions compared to wild-type mice. In Clock-mutant mice, suppression of Acs14 and Fabp1 mRNA in the liver under high-fat diet conditions may have attenuated the accumulation of triglycerides in the liver compared to wild-type mice under the same conditions. In conclusion, the authors demonstrate that mice with a Clock mutation showed less triglyceride accumulation in the liver through the suppression of Acs14 and Fabp1 gene expression when fed a high-fat diet compared to wild-type mice fed the same diet.