Kudo Takashi, Tamagawa Toru, Kawashima Mihoko, Mito Natsuko, Shibata Shigenobu
Department of Physiology and Pharmacology, School of Science and Engineering, Waseda University, Tokyo, Japan.
J Biol Rhythms. 2007 Aug;22(4):312-23. doi: 10.1177/0748730407302625.
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 Acsl4 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 Acsl4 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 Acsl4 and Fabp1 gene expression when fed a high-fat diet compared to wild-type mice fed the same diet.
能量平衡受昼夜节律控制，该节律使能量摄入与消耗同步。转录因子CLOCK是分子昼夜节律钟的关键组成部分，控制多种节律，如运动活动、体温和代谢功能的节律。本研究的目的是利用Clock基因敲除小鼠了解肝脏脂质代谢过程中Clock基因的功能。将具有ICR背景的Clock基因敲除小鼠喂食高脂饮食13周，并检测肝脏甘油三酯、血清甘油三酯和血清游离脂肪酸水平。与喂食高脂饮食的野生型小鼠相比，喂食高脂饮食的Clock基因敲除小鼠肝脏中甘油三酯含量的增加显著减少。野生型小鼠肝脏中Acsl4和Fabp1 mRNA水平呈现昼夜节律。相比之下，与野生型小鼠相比，在正常和高脂饮食条件下，Clock基因敲除小鼠肝脏中Acsl4和Fabp1基因表达的昼夜节律减弱。在Clock基因敲除小鼠中，与相同条件下的野生型小鼠相比，高脂饮食条件下肝脏中Acsl4和Fabp1 mRNA的抑制可能减弱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，Clock基因敲除小鼠在喂食高脂饮食时，通过抑制Acsl4和Fabp1基因表达，肝脏中甘油三酯积累较少。
