Minana-Solis M C, Angeles-Castellanos M, Feillet C, Pevet P, Challet E, Escobar C
Departamento de Anatomia, Facultad de Medicina Universidad Nacional Autonoma de Mexico, Mexico, D F.
Chronobiol Int. 2009 Jul;26(5):808-20. doi: 10.1080/07420520903044240.
Restricted feeding schedules (RFS) entrain digestive, hormonal, and metabolic functions as well as oscillations of clock genes, such as Per1 and Per2, in peripheral organs. In the brain, in particular the hypothalamus, RFS induce and shift daily rhythms of Per1 and Per2 expression. To determine whether RFS affect clock genes in extra-SCN oscillators in a uniform manner, the present study investigated daily rhythms of Per1, Per2, and Bmal1 expression in various hypothalamic regions. Wistar rats were entrained to daily RFS (2 h food access starting at ZT6, RFS) or fed ad libitum (C) for three weeks. Brains were sampled every 3 h starting at ZT0, and were processed with in situ hybridization. In response to RFS, Per1 expression showed a 3 h phase advance in the suprachiasmatic nucleus (SCN), while Per2 and Bmal1 remained unaffected. Per1 was triggered at ZT6, anticipating food access in both arcuate (ARC) and dorsomedial nuclei (DMH), and was unaffected in the ventromedial (VMH) and paraventricular (PVN) nuclei. In contrast, Per2 expression during RFS showed a marked postprandial peak in the PVN, was unchanged in the ARC, and was down-regulated in the DMH and VMH. The temporal patterns of Bmal1 expression were not significantly modified in RFS rats. RFS differentially affected clock-gene expression (phase change, up- or downregulation) depending on the combination of hypothalamic nuclei and targeted genes. Present data highlight that metabolic or temporal cues elicited by feeding modify the temporal organization in the hypothalamus and are not exclusive for a food-entrained oscillator.
限时进食时间表（RFS）可调节外周器官的消化、激素和代谢功能以及生物钟基因（如Per1和Per2）的振荡。在大脑中，特别是下丘脑，RFS可诱导并改变Per1和Per2表达的每日节律。为了确定RFS是否以统一方式影响视交叉上核（SCN）外振荡器中的生物钟基因，本研究调查了下丘脑各区域中Per1、Per2和Bmal1表达的每日节律。将Wistar大鼠分为两组，一组按照每日RFS（从ZT6开始有2小时进食时间，即RFS组），另一组自由进食（C组），持续三周。从ZT0开始，每3小时采集一次大脑样本，并进行原位杂交处理。对RFS的反应中，视交叉上核（SCN）中Per1的表达提前了3小时，而Per2和Bmal1不受影响。Per1在ZT6被触发，在弓状核（ARC）和背内侧核（DMH）中都先于进食时间出现，而在腹内侧核（VMH）和室旁核（PVN）中不受影响。相比之下，RFS期间Per2的表达在PVN中显示出明显的餐后峰值，在ARC中不变，在DMH和VMH中下调。RFS大鼠中Bmal1表达的时间模式没有显著改变。RFS根据下丘脑核团和目标基因的组合，对生物钟基因表达产生不同影响（相位变化、上调或下调）。目前的数据表明，进食引发的代谢或时间线索会改变下丘脑的时间组织，且并非食物诱导振荡器所特有。
