Peripheral Circadian Oscillators: Time and Food - Progress in Molecular Biology and Translational Science - page 90

Also challenging this observation is a recent study of the group of Hogenesch
using a brain-specific rescue of Clock that revealed that this rescued the
rhythm of many liver genes and consequently demonstrated a so-called
system-driven rhythm 52 supporting the notion that indeed many different
SCN-driven systems other than peripheral clock genes are able to drive
peripheral oscillators.
The complexity and diversity of the processes driven by the SCN require
a fine tuning and synchronization of these different rhythms. For this reason,
one would suggest that the SCN is driving the rhythm of the peripheral
oscillators and that peripheral oscillators have a way to talk back to the
SCN in order to allow it to function as one homeostatic system.
6. TIMING BY FOOD?
As early as clock genes were described in peripheral tissues, it became
clear that in addition to the SCN, they could be entrained by food-related
signals. Shifting feeding schedules toward the day in mice changed circadian
gene expression in liver, kidney, heart, and pancreas but not in the SCN. 4
This effect was confirmed in the liver of transgenic mice in which the Per1
gene promoter had been linked to a luciferase reporter. Daytime feeding
rapidly entrained the liver, shifting its phase by 10 h toward the day within
3 days. 3 Short 2-4 h restricted feeding schedules in arrhythmic mice due to a
bilateral SCN lesion also restored circadian rhythmicity in some clock genes
in the liver. 5 Finally, daytime-restricted feeding in nocturnal rodents
induced and inverted the phase of clock gene expression; thus, feeding
rhythms appeared to be a dominant Zeitgeber for the entrainment of hepatic
clock genes. Importantly, feeding time had no effect on the expression of
clock genes in the SCN, suggesting that a daytime-feeding regime
completely uncouples the phases of the clock genes in the liver from those
in the biological clock. 4,5,53 It is important to realize that, in spite of the fact
that the overall clock gene expression in the SCN might be unaltered,
within the SCN changes in food regime may induce important regional
changes that allow the circadian system to adapt to these circumstances; such
changes may go undetected by overall analysis. 54,55
The possible signaling cue elicited by feeding schedules to peripheral
cells is suggested to have multiple origins. Several circulating metabolic
and hormonal factors, originally controlled by the SCN, are also dependent
on food intake, including glucose, free fatty acids, glucocorticoids, thyroid
hormones, and others. Several exhibit shifted food-entrained rhythms when