不同摄食模式对小鼠生物钟及脂质代谢基因节律的影响

目的：研究不同摄食模式对ICR小鼠脑内及肝脏生物钟基因表达的影响。方法：将90只雄性ICR小鼠分为自由摄食组、明期摄食组和暗期摄食组，每组30只，12 h与12 h明-暗交替条件下喂养两周。以4 h为间隔，每组分别在08∶00、12∶00、16∶00、20∶00、0∶00、04∶00时间点各处死5只小鼠取脑和肝脏，检测各时间点小鼠脑和肝脏组织内各生物钟及钟控基因的表达。结果：与肝脏相比，脑内节律振荡器更易受摄食方式的影响；且暗期摄食使脑内Cry2、Per1、Per2的峰值分别下调了81.8%、76.7%、85.9%，对脑内节律振荡器的影响更为显著。而暗期摄食条件下肝脏各生物钟基因的表达模式与自由摄食条件下相似。此外，与自由摄食组相比，明、暗期摄食条件下，Rev-erbα和Dbp的峰值均明显下调（下调了50%、90.5%和70.6%、64.3%），且Rev-erbα、Dbp的表达模式在两种摄食条件下相反。明、暗期摄食条件下，肝脏脂质代谢基因SREBP1-c、PPARα、FAS、CPT的表达模式不同，且明、暗期摄食均下调了肝脏脂质代谢基因SREBP1-c和PPARα的表达水平（分别下调了81.8%、75.0%和4.75%、79.2%）。结论：改变固有的摄食方式会夹带小鼠脑和肝脏内节律振荡器，肝脏中各节律振荡器均与摄食（时间）相偶联。

Effects of feeding mode on biological clock and circadian expression of lipid metabolism-related genes in mice

Objective: To explore the effects of feeding mode on biological clock and circadian expression of lipids metabolism-related genes in mice. Methods: Ninety healthy male ICR mice were divided into 3 groups with 30 in each: ad libitum-feeding, daytime-feeding and nighttime-feeding groups, in a 12 h to 12 h light- dark cycle. After two weeks of feeding the animals was sacrificed in batches (5 in each batch) at 4, 8, 12, 16, 20 and 24 h, the circadian expression of lipids metabolism-related genes in the liver and brain was detected by real-time quantitative RT-PCR at 6 time points. Results: The circadian oscillator in the brain was more sensitive to alteration of feeding mode than that in the liver, nighttime feeding decreased peak mRNA levels of Cry2, Per1, and Per2 (5.5, 4.3 and 7.1 folds, respectively) in the brain. However, there was no difference in the expression rhythm of hepatic clock genes between nighttime-feeding and ad libitum group. In addition, changed feeding mode significantly decreased the peak value of Rev-erbα (2 folds for daytime feeding, 3.4 folds for nighttime feeding) and Dbp (10.6 folds for daytime feeding, 2.8 folds for nighttime feeding), which two had opposite expression mode in different feeding modes. Different expression rhythm of lipid metabolism-related genes SREBP1-c, PPARα, FAS, and CPT was shown with decreased mRNA expression levels of SREBP1-c and PPARα in daytime feeding (5.5 folds,4 folds) and nighttime feeding (4.4 folds, 4.8 folds). Conclusion: Changing the feeding mode could entrain circadian oscillators both in the brain and liver. What is more, hepatic circadian oscillators couple with the feeding time．