Circadian Clocks, Food Intake, and Metabolism - Progress in Molecular Biology and Translational Science - page 116

Among stimuli capable of resetting the central clock, light is the most
potent ( Fig. 5.2 ) . Light cues are first perceived by the retina that contains
a circadian clock. 90 Photosensitive ganglion cells containing the photo-
pigment melanopsin send fibers that project to the SCN, either directly
via the retinohypothalamic tract or indirectly via the intergeniculate leaflet
of the thalamus. 91,92 The way the SCN clock is synchronized to light is char-
acterized by a photosensitive daily period (mainly at night) during which
light cues can shift the clock, while the temporal window around midday
defines a period during which light has no phase-resetting effect. 91
A newly identified modulator of photic resetting in the SCN is the meta-
bolic transcription factor, PPAR b / d . 93
Under light-dark cycle, light can indirectly affect rhythmicity in periph-
eral organs through signals coming from the SCN via sympathetic projec-
tions. This is the case for plasma glucose that, in addition to its circadian
control, can be increased by light exposure or stress. 94,95 Furthermore, as
already evoked for food intake, the apparent daily sleep-wake cycle can also
be modulated by direct, clock-independent responses to light, called “mas-
king” in the circadian field. 96,97
Daily rhythmicity of release of hormones in the bloodstream is the rule,
rather than the exception. In nocturnal rats, plasma levels of both insulin and
leptin increase during the early activity period (night). 98-100 Because sup-
rachiasmatic lesions in rodents abolish this rhythmicity (i.e., hormonal
rhythms become flattened, usually around the mean level), this reveals a
control by the suprachiasmatic clock. 98,100 Studies in functional neuroanat-
omy have shown that the suprachiasmatic control of endocrine rhythmicity
is largely mediated by the sympathetic innervation via hypothalamic relays
(i.e., paraventricular and dorsomedial nuclei, and subparaventricular region)
receiving vasopressinergic, glutamatergic, and GABAergic inputs from the
master clock. 3
In humans, hormonal rhythmicity is known to depend not only on cir-
cadian clocks but also on food intake, sleep, and light. To limit these
so-called confounding effects from a strict circadian point of view, human
subjects can be maintained for almost 2 days awake to avoid sleep-induced
effects, fed hourly isocaloric meals to avoid synchronizing effects of daily
mealtime, and in constant dim light to prevent direct or synchronizing
effects of light (this experimental situation is the so-called condition of con-
stant routine). Using this paradigm, plasma leptin and insulin show a peak
around the minimal body temperature and close to the usual time of