Peripheral Circadian Oscillators: Time and Food - Progress in Molecular Biology and Translational Science - page 89

By considering the possible mechanism that drives peripheral oscillators, it is
important to keep in mind that organs can exchange metabolic information
via hormones and the modulation of the autonomic nervous system, with or
without the central nervous system as interface. 47-50 The relevance of the
interaction and exchange of information between the different organs is that,
at many different places in our body and brain, metabolic information can be
gathered and integrated by influencing the functionality of this network. It
will be clear that under normal conditions, all these different elements, hor-
mones, metabolites, and autonomic nervous system, act in synchrony
enforcing each other's action. Consequently, removing one of these factors
will not change the oscillations as other stimuli remain in place. This coop-
eration between different factors makes it difficult to estimate the individual
contribution of, for example, corticosterone as compared to sympathetic
input. One would need to know and remove all other contributors (like
food intake or temperature) to be able to make such approximation. Later,
we will come back to this point by discussing the effect of changing only the
food availability to another circadian time point on the expression of clock
and metabolic genes.

5. SYNCHRONIZATION OF THE CIRCADIAN SYSTEM
BY THE SCN

We have seen that we have to consider the peripheral oscillators and
the SCN function as one system that is in perfect balance. Consequently,
under normal conditions, the peripheral oscillators are strongly driven by
the SCN and SCN-driven processes. The loss of one rhythmic input, for
example, the rhythm in corticosterone, would not mean that all rhythmicity
is lost because many other inputs to the organ would remain in place. In
contrast to this seems the proposed organization at the cellular level where
up till now attention has been focused on the role of the clock genes and
their position has been emphasized as pivotal also for the rhythmicity at
the organ level. For example, the observations of Kornmann et al.

51

who
used mice with a conditionally active liver clock, in which REV-ERBalpha
represses (among others) the transcription of the essential core clock gene
Bmal1 and reported that most liver genes lost their rhythm and just a few
genes remained rhythmic. The authors concluded, therefore, that the
rhythm of most liver genes would depend on the rhythmicity of BMAL1
and thus on the functionality of hepatocyte clocks. In contrast to this state-
ment was their observation that Per2 expression kept a strong rhythmicity.