Peripheral circadian oscillators in mammals: Time and food
Peripheral circadian oscillators in mammals: Time and food
复制标题
DOI：
10.1177/0748730403018003007
复制
发表时间：
2003-06-01
影响因子：
3.5
通讯作者：
Brown, SA
中科院分区：
文献类型：
--
作者：
Schibler, U;Ripperger, J;Brown, SA
来自哺乳动物组织的外周细胞虽然完全能够产生昼夜节律，但对光不敏感，因此必须被非光信号所携带。进食时间是哺乳动物外周生物钟的主要时间表：夜间实验室啮齿动物的白天进食完全逆转了许多组织（包括肝脏、心脏、肾脏和胰腺）中的昼夜节律基因表达，但对SCN起搏器没有影响。因此，在完整的动物中，SCN主要通过由行为休息-活动周期施加的时间进食模式来调节外周时钟是合理的。此外，体温节律本身依赖于进食模式和休息-活动周期，可以维持体内和体外的昼夜节律和时钟基因活性。SCN还可以通过直接的化学途径影响外周组织中节律性基因表达的时相。事实上，许多化学信号诱导组织培养细胞中的昼夜节律基因表达。其中一些已被证明在注射到完整的动物中时会引起相移，因此是生理相关时序线索的候选者。虽然SCN对光的响应被严格地门控为仅在夜间响应，但外围振荡器可以在整个白天发生化学相移。例如，注射地塞米松，糖皮质激素受体激动剂，重置在整个24小时的一天中的昼夜肝脏基因表达的相位。考虑到能够影响外周时钟的代理令人困惑的阵列，识别SCN用于同步外周时钟的生理相关代理显然将是一项艰巨的任务。尽管如此，我们认为，可以用来解决这一诱人问题的实验性制度现在已经存在。
Peripheral cells from mammalian tissues, while perfectly capable of circadian rhythm generation, are not light sensitive and thus have to be entrained by nonphotic cues. Feeding time is the dominant zeitgeber for peripheral mammalian clocks: Daytime feeding of nocturnal laboratory rodents completely inverts the phase of circadian gene expression in many tissues, including liver, heart, kidney, and pancreas, but it has no effect on the SCN pacemaker. It is thus plausible that in intact animals, the SCN synchronizes peripheral clocks primarily through temporal feeding patterns that are imposed through behavioral rest-activity cycles. In addition, body temperature rhythms, which are themselves dependent on both feeding patterns and rest-activity cycles, can sustain circadian, clock gene activity in vivo and in vitro. The SCN may also influence the phase of rhythmic gene expression in peripheral tissues through direct chemical pathways. In fact, many chemical signals induce circadian gene expression in tissue culture cells. Some of these have been shown to elicit phase shifts when injected into intact animals and are thus candidates for physiologically relevant timing cues. While the response of the SCN to light is strictly gated to respond only during the night, peripheral oscillators can be chemically phase shifted throughout the day. For example, injection of dexamethasone, a glucocorticoid receptor agonist, resets the phase of circadian liver gene expression during the entire 24-h day. Given the bewildering array of agents capable of influencing peripheral clocks, the identification of physiologically relevant agents used by the SCN to synchronize peripheral clocks will clearly be an arduous undertaking. Nevertheless, we feel that experimental systems by which this enticing problem can be tackled are now at hand.