Chronobiology and Obesity: The Orchestra Out of Tune

Marta Garaulet; Purificación Gómez-Abellán; Juan Antonio Madrid


Clin Lipidology. 2010;5(2):181-188. 

In This Article

A Biological Explanation of this Orchestral Failure

Chronodisruption can be the result of alterations of different levels in this physiological orchestra. Impairments can be present in the inputs such as the light–dark cycle or the feeding time; in the central pacemaker (SCN); or in the outputs related to melatonin and corticoids.


It has been demonstrated that light deficiency, whether a result of improper timing, suboptimal spectrum or insufficient intensity, may contribute to medical conditions associated with CD.[29]

Feeding Time

Feeding time is also considered one of the most important external synchronizers or zeitgeber for peripheral oscillators. Thus, unusual feeding times can also contribute to some of the effects of CD. For example, subjects with a nocturnal life style, characterized by late awakening, skipping breakfast and late dinner, present hyperglycemia during the night while nocturnal leptin and melatonin were reduced.[30] Therefore, nocturnal life is likely to be one of the risk factors to the health of modern people, including night eating syndrome, obesity and diabetes.


Regarding the pacemaker contribution to CD, it had been originally suggested that the existence of different rates of synchronization of biological variables is the cause of jet-lag and shift-work-induced CD. In fact, a transitory status of internal desynchronization is produced as a consequence of the different coupling strengths between SCN and peripheral oscillators or the differential influence of external synchronizers (feeding or light).

Chronodisruption can also be produced by the alteration of the core machinery of the molecular circadian clock. BMAL1, PER2 and CLOCK, among other Clock proteins, have a specific role in the organism's physiology, in addition, to their role in the circadian molecular.[31] It was in 2005 that it was demonstrated for the first time that impairments in the Clock gene were significantly related to obesity. On one hand, Turek et al. found that homozygous Clock mutant mice had a greatly attenuated diurnal feeding rhythm, were hyperphagic and obese, and developed a metabolic syndrome of hyperleptinemia, hyperlipidemia, hepatic steatosis, hyperglycemia and hypoinsulinemia.[32] On the other hand, Ando et al. demonstrated that obesity was related to CD in experimental models.[33] Indeed, the rhythmic expression of clock genes and adipocytokines in adipose tissue was more attenuated as it increased the degree of obesity of the mice. However, significant controversy exists with regard to these aspects; Kennaway demonstrated that Clock (Delta 19) mutation with arrhythmic Clock gene expression in the liver and skeletal muscle did not cause obesity and increased insulin sensitivity.[34] However, serum triglycerides and free fatty acids have been found to be significantly lower in circadian Clock mutant mice.[35]


The third element that can be the cause of CD is the alteration of the outputs of the circadian system, which include among others, the aforementioned melatonin (e.g, TGF-α and prokineticine 2).[17,18] Melatonin is a well-known antioxidant anti-inflammatory and possibly an epigenetic regulator that directly scavenges free radicals.[36] It has also been related to obesity alteration, acting as a protective hormone. Indeed, it reduces blood pressure and improves glucose metabolism by restoring the vascular action of insulin.[37]


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