Circadian Clocks, Food Intake, and Metabolism - Progress in Molecular Biology and Translational Science - page 117

awakening, respectively. 101 Similarly, plasma fatty acids are also found to be
under circadian control, with higher levels during subjective daytime. 102
Contrary to the high sensitivity of peripheral clocks to the feeding cues,
the suprachiasmatic clock of food-restricted animals under a light-dark cycle
appears to be buffered against any synchronizing effect of mealtime, as
shown with the lack of phase shift of either the circadian rhythm of firing
rate or clock gene expression in the SCN. 70,103,104 This does not mean,
however, that feeding-associated signals do not reach at all the sup-
rachiasmatic cells. When the photic synchronizer is absent, that is in constant
dark or constant light, timed meals can, although not systematically, entrain
the suprachiasmatic clock. 19,22 Diurnal parenteral nutrition and in vivo glu-
cose infusion produce shifts of clock gene oscillations in the master clock. 105
Calorie restriction and starvation both lead to a major mobilization of
energy stores and affect the timing of the sleep-wake cycle. When chal-
lenged with calorie restriction, nocturnal animals become active during their
usual sleep period (i.e., they become partially diurnal), independently of the
time of feeding. 106,107 Conversely, calorie-restricted diurnal rodents change
their behavioral timing of activity to nighttime. 108 These modifications in
behavioral timing in case of negative energy balance are due in part to
the fact that metabolic cues associated with calorie restriction affect the sup-
rachiasmatic clock machinery and its synchronization to light. 107,108
A ketogenic diet is another example of negative energy balance leading
to body mass loss, lipid mobilization, and phase-advanced sleep-wake
cycle. 109 Nocturnal mice, that have to work for getting food with increasing
levels of workload over days, become also partially diurnal. Interestingly, the
switch from nocturnal to diurnal pattern of activity coincides with a gradual
shift toward a negative energy balance. 110 Whatever the cause, chronic
hypocaloric conditions may ultimately change the cellular metabolic state
of suprachiasmatic cells, therefore, altering the mechanisms of circadian
oscillations. Alternatively or in combination, circulating metabolites (glu-
cose, nonesterified fatty acids) and metabolic hormones may modulate pho-
tic resetting according to the metabolic status.
A daily palatable snack in addition to regular food (chow pellets) pro-
vided ad libitum is able to entrain behavioral rhythms of rats and mice in con-
stant darkness conditions. 111,112 In mice, ingestion of the attractive and
palatable snack activates both the reward and arousal systems in the brain,
suggesting that the modulatory effects on the master clock involve somehow
dopaminergic and orexinergic pathways. 112 The timing of suprachiasmatic