Diet-induced insulin resistance state disturbs brain clock processes and alters tuning of clock outputs in the Sand rat, Psammomys obesus.

Reciprocal interactions closely connect energy metabolism with circadian rhythmicity. Altered clockwork and circadian desynchronization are often linked with impaired energy regulation. Conversely, metabolic disturbances have been associated with altered autonomic and hormonal rhythms. The effects of high-energy (HE) diet on the master clock in the suprachiasmatic nuclei (SCN) remain unclear.This question was addressed in the Sand rat (Psammomys obesus), a non-insulin-dependent diabetes mellitus (NIDDM) animal model. The aim of this work was to determine whether enriched diet in Psammomys affects locomotor activity rhythm, as well as daily oscillations in the master clock of the SCN and in an extra-SCN brain oscillator, the piriform cortex. Sand rats were fed during 3 months with either low or HE diet. Vasoactive intestinal peptide (VIP), vasopressin (AVP) and CLOCK protein cycling were studied by immunohistochemistry and running wheel protocol was used for behavioral analysis. High energy feeding dietary triggered hyperinsulinemia, impaired insulin/glucose ratio and disruption in pancreatic hormonal rhythms. Circadian disturbances in hyper-insulinemic animals include a lengthened rest/activity rhythm in constant darkness, as well as disappearance of daily rhythmicity of VIP, AVP and the circadian transcription factor CLOCK within the suprachiasmatic clock. In addition, daily rhythmicity of VIP and CLOCK was abolished by HE diet in a secondary brain oscillator, the piriform cortex. Our findings highlight a major impact of diabetogenic diet on central and peripheral rhythmicity. The Psammomys model will be instrumental to better understand the functional links between circadian clocks, glucose intolerance and insulin resistance state.

Light-induced c-Fos expression in the SCN and behavioural phase shifts of Djungarian hamsters with a delayed activity onset.

C-Fos expression in the suprachiasmatic nucleus (SCN) and phase shifts of the activity rhythm following photic stimulation were investigated in Djungarian hamsters (Phodopus sungorus) of two different circadian phenotypes. Wild-type (WT) hamsters display robust daily patterns of locomotor activity according to the light/dark conditions. Hamsters of the DAO (delayed activity onset) phenotype, however, progressively delay the activity onset, whereas activity offset remains coupled to "light-on". Although the exact reason for the delayed activity onset is not yet clarified, it is connected with a disturbed interaction between the light/dark cycle and the circadian clock. The aim was to test the link between photoreception and the behavioral output of the circadian system in hamsters of both phenotypes, to get further insight in the underlying mechanism of the DAO phenomenon. Animals were exposed to short light pulses at different times during the dark period to analyze phase shifts of the activity rhythm and expression of Fos protein in the SCN. The results indicate that the photosensitive phase in DAO hamsters is shifted like the activity onset. Also, phase shifts were significantly smaller in DAO hamsters. At the same time, levels of Fos expression did not differ between phenotypes regarding the circadian phase. The results provide evidence that the shifted photosensitivity of the circadian system in DAO hamsters does not differ from that of WT animals, and lead us to conclude that processes within the SCN that enable light information to reset the circadian pacemaker might offer an explanation for the DAO phenomenon.

Seasonal variations of clock gene expression in the suprachiasmatic nuclei and pars tuberalis of the European hamster (Cricetus cricetus).

In mammals, day length (photoperiod) is read and encoded in the main circadian clock, the suprachiasmatic nuclei (SCN). In turn, the SCN control the seasonal rhythmicity of various physiological processes, in particular the secretion pattern of the pineal hormone melatonin. This hormone then operates as an essential mediator for the control of seasonal physiological functions on some tissues, especially the pars tuberalis (PT). In the European hamster, both hormonal (melatonin) and behavioral (locomotor activity) rhythms are strongly affected by season, making this species an interesting model to investigate the impact of the seasonal variations of the environment. The direct (on SCN) and indirect (via melatonin on PT) effect of natural short and long photoperiod was investigated on the daily expression of clock genes, these being expressed in both tissues. In the SCN, photoperiod altered the expression of all clock genes studied. In short photoperiod, whereas Clock mRNA levels were reduced, Bmal1 expression became arrhythmic, probably resulting in the observed dramatic reduction in the rhythm of Avp expression. In the PT, Per1 and Rev-erbalpha expressions were anchored to dawn in both photoperiods. The daily profiles of Cry1 mRNA were not concordant with the daily variations in plasma melatonin although we confirmed that Cry1 expression is regulated by an acute melatonin injection in the hamster PT. The putative role of such seasonal-dependent changes in clock gene expression on the control of seasonal functions is discussed.

Conflicting effects of exercise on the establishment of a short-photoperiod phenotype in Syrian hamster.

In the Syrian hamster, winter seasonal inhibition of reproduction occurs in response to decreasing day length. This inhibitory response is modulated by nonphotic cues. In particular, access to a running wheel has been shown to produce incomplete gonadal regression. The present study sought to determine whether this occurs as a consequence of wheel effect on adaptation of the circadian system to short days or whether downstream physiological responses are involved. Short-day adaptation of the circadian clock, which is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, was tested by lengthening the photosensitive phase of the SCN (assayed by light-induced c-Fos expression in the SCN) as a parameter. We found that wheel-running activity does not inhibit the integration of the photoperiodic change by the SCN even if complete testicular regression is prevented. Moreover, this exercise was even capable of accelerating the lengthening of the photosensitive phase after the transfer to short day length. Thus, although wheel-running activity inhibits the short photoperiod-induced gonadal regression, it acts on the SCN to accelerate the integration of the photoperiodic change by the biological clock.