10.1177/0748730403253381ARTICLEJOURNAL OF BIOLOGICAL RHYTHMS / June 2003Schibler et al. / CIRCADI N OSCILLATORS IN MAMMALS PERIPHERY Peripheral Circadian Oscillators in Mammals: Time and Food

Abstract Peripheral cells from mammalian tissues, while perfectly capable of cir-cadian rhythm generation, are not light sensitive and thus have to be entrained by nonphotic cues. Feeding time is the dominant zeitgeber for peripheral mam-malian 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 primar-ily 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 circa-dian, 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 tis-sue culture cells. Some of these have been shown to elicit phase shifts when injected into intact animals and are thus candidates for physiologically relevan