Forced desynchronization of the circadian system through chronic jet lag affects metabolic function

CASIRAGHI L; ALZAMENDI A; GIOVAMBATTISTA A; GOLOMBEK D

Lyon

Congreso; 11e Colloque Societé des Neurosciences; 2013

Societé des Neurosciences

Circadian disruption by shift-work and jet-lag has been established as a health hazard in both humans and in animal models. The mechanisms by which these conditions lead to such a wide range of deleterious effects are still unclear. Internal desynchronization of physiological variables has been proposed as a potential underlying cause. We developed and characterized a model of forced desynchronization of the circadian system, based on a chronic jet-lag (CJL) schedule consisting in 6 hour advances of the light-dark (LD) cycle every 2 days (ChrA). Moreover, we suggest that this is due to the disruption of the coupling of the ventrolateral and dorsomedial regions of the master clock in the suprachiasmatic nuclei (SCN). The SCN clock tightly controls the timing of peripheral organs and metabolism, and we hypothesized that metabolic disturbances should be present in the ChrA model. METHODS; We evaluated several metabolic variables (weight gain, food intake, leptin and triglycerides blood levels, and amount and histology of fat tissue) in mice subjected to ChrA. Restricting feeding times to periods of darkness in ChrA was assayed as a potential therapy for the circadian disruption. Animals under a CJL schedule of delays of the LD cycle (ChrD), which does not produce desynchronization, were also studied. RESULTS: Body weight gain was significantly increased in animals under ChrA as compared to controls, an effect evident from the first week to over 60 days from ChrA start. Epididymal fat was also increased in ChrA mice. While restricting feeding times to the dark phase resulted in decreased body weight gain, it appears to be linked to varying food intake. There was no effect of the ChrD schedule on body weight gain as compared to controls. DISCUSSION: We found that disruption of the biological rhythms through ChrA disturbs metabolic function at different levels. The effects seem to be linked to forced desynchronization of the circadian system, as no disturbances were detected under the less disrupting ChrD schedule, supporting the notion that advance and delay jet-lag have asymmetric effects on physiology. In conclusion, we confirm the ChrA model as a useful tool for studying health issues related to the stress of normal circadian function and strategies to prevent and overcome these hazards.