Peripheral Circadian Oscillators: Time and Food - Progress in Molecular Biology and Translational Science - page 97

Figure 4.2 In a model with food during the rest period, the relationship between clock

and metabolic genes changes. Animals with food ad libitum (CTRL) or during the active
period (FAA) have clear rhythms in NAD, Ppara, and Pparg that are in opposite to the
rhythm of Bmal1. However, when food is restricted to the rest period (FRP), this relation-
ship is lost for NAD or flattened for PPARa and PPARg. See text and Salgado et al. (2013)
for further details.

has a proposed feedback role on clock genes by inhibiting Clock and

24 The observation of a simultaneous decrease in SIRT1, together
with the decrease and loss of rhythm in Per2 and Nampt , suggests an impor-
tant disturbance of these three elements in the link between the core clock
and metabolism, in circadian misaligned animals. The uncoupling of the
rhythm of Nampt from that of Clock and Bmal1 raises the question which
other cellular messengers will form the link between food (i.e., glucose
uptake), metabolic genes, and clock genes and demonstrate the necessity
of using physiological models in order to understand and validate proposed
interactions of the molecular networks in the cell. In this respect, it might be
worth considering that peroxiredoxins, which are evolutionarily extremely
conserved molecules associated with the oxidative state of the cell, show a
rhythm in their oxidation level which, in turn, is associated with the met-
abolic cycle may influence the synthesis of NAMPT. 93

Bmal1.