Circadian Clocks, Food Intake, and Metabolism - Progress in Molecular Biology and Translational Science - page 109

in these neural structures, 14-16 their functional implication in the daily
rhythm of ingestive behaviors remains to be established.
Bilateral lesions of the SCN as well as knife-cuts around them abolish
circadian rhythmicity of the feeding/fasting cycle, indicating that the sup-
rachiasmatic clock controls the circadian rhythm of feeding. 17,18 As afore-
mentioned, because suprachiasmatic lesions also produce arrhythmicity of
sleep-wake cycle, the concomitant loss of feeding rhythm may partly be
an indirect consequence of behavioral arrhythmicity (in that view, des-
tructured sleep timing would be the direct cause of the destructured pattern
of food intake). There are experimental arguments outlined below,
suggesting that a feeding-entrainable system outside the SCN may also par-
ticipate in the daily rhythm of food foraging/intake ( Fig. 5.1 ) .
Timing of food availability has a major impact on overt rhythmicity.
When food access is limited to a few hours every day at the same time (tem-
poral restricted feeding), animals display food-anticipatory activity, that is, a
bout of arousal accompanied with food-appetitive behaviors and physical
activity prior to the expected food presentation. 19 Such a rhythmic behavior
anticipating food presentation on a daily basis is manifest not only in food-
restricted adult animals but also in pups nursed daily by the mother shortly
once a day. 20,21 Other physiological parameters such as body temperature
and corticosterone release also rise before food presentation, in phase with
anticipatory behavior. 19,22 In rodents arrhythmic after suprachiasmatic
lesions, temporal restricted feeding provides timing cues to the rest of the
circadian system, thus restoring behavioral rhythmicity via daily food-
anticipatory activity, hormonal rhythmicity, and/or sympathetic activa-
tion. 22,23 There are food-entrainable clocks throughout the brain that likely
define a multi-oscillatory network coupling several neural oscillators most
sensitive to feeding cues. Albeit the anatomic brain substrate that initiates
food-anticipatory behavioral activity has been difficult to ascertain, possibly
due to its distributed nature, experimental data favor the participation of
some structures in the metabolic hypothalamus, the brainstem, and

cerebellum. 19,24-26
Alterations in the diurnal pattern of feeding have been detected in mice
with functionally impaired clock genes. The daily pattern of food intake
under a light-dark cycle is markedly attenuated in Clock mutant mice and
in mice with adipocyte-specific deletion of Bmal1 , food intake during day-
time being found greater than that in wild-type mice. 27,28 Other mutations
of clock genes, such Rev - erb a , do not impair daily pattern of feeding. 29 In
mammals, a major modulator of the ultradian meal pattern during the