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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
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-
rats, the amplitude of clock gene expression is dampened in the liver, but
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
with increased intake in the second half of the light period, and greater
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
feeding behavior is lengthened, due to increased food intake during the late
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