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been shown to have adverse effects on glucose metabolism, such as impair-
ment of glucose tolerance and insulin sensitivity, both being major risk fac-
tors for type 2 diabetes, and sleep deprivation leads to an increase in hunger
feeling. 147 Shorter periods of sleep will also increase the daily period avail-
able for eating.
Together, these data reveal that unusual timing of light exposure and/or
meals in healthy individuals are major contributors of circadian mis-
alignment, perturbing clock rhythmicity, and sleep homeostasis, whose
alterations increase the likelihood of metabolic risk factors.
3.2. Metabolic pathologies are frequently associated with
circadian disturbances
Now will be described some of the circadian abnormalities observed in
genetic and experimental models of obesity and diabetes.
The Zucker rat is an animal model of genetic obesity, caused by a muta-
tion ( fa ) in the gene encoding the receptor of leptin, an anorexigenic hor-
mone synthesized by adipose tissue and acting notably on the metabolic
hypothalamus. The fa mutation leads to hyperphagia and excessive adiposity.
In addition, the Zucker rat maintained under a light-dark cycle displays
alterations in daily timing, characterized by phase advances of feeding, loco-
motor activity and body temperature rhythms. 148,149 In these leptin-resistant
rats, the amplitude of clock gene expression is dampened in the liver, but
neither in the white adipose tissue nor in the SCN. 150 Mice carrying the
ob mutation become obese because their adipocytes cannot synthesize leptin.
These mice have an increased ultradian activity at the expense of the circa-
dian pattern and an increased daytime activity, while the endogenous period
is not affected. 151 The daily pattern of feeding is modified in ob / ob mice,
with increased intake in the second half of the light period, and greater
energy intake in the early and late parts of the dark period. 152 The amplitude
of clock gene oscillations in ob / ob mice is decreased in the liver and adipose
tissue, but not in the SCN. These circadian abnormalities are observed
before any detectable metabolic dysfunctions, ruling out a causal role of obe-
sity in the appearance of the circadian perturbations. 153
Experimental studies in mice have shown that excess energy intake of a
high-fat diet is associated with several circadian abnormalities. The period of
the endogenous clock suprachiasmatic is elongated relative to that of control
mice fed with a standard chow diet. 137,154 Furthermore, the daily period of
feeding behavior is lengthened, due to increased food intake during the late
part of usual period of rest (daytime in mice). 154 In addition, daily variations
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