Circadian and photic regulation of clock and clock-controlled proteins in the suprachiasmatic nuclei of calorie-restricted mice.

In mammals, behavioural and physiological rhythms as well as clock gene expression in the central suprachiasmatic clock (SCN) are phase-shifted by a timed calorie restriction (T-CR; animals receiving at midday 66% of their daily food intake). The molecular mechanism of SCN depends on feedback loops involving clock genes and their protein products. To understand how T-CR mediates its synchronizing effects, we examined the rhythmic expression of three clock proteins, PERIOD (PER) 1, 2 and CLOCK, and one clock-controlled protein (i.e. vasopressin; AVP) in the SCN of mice either fed ad libitum (AL) or with T-CR. Moreover, we evaluated expression of these proteins in the SCN of AL and T-CR mice following a 1-h light pulse. The results indicate that, while PER1 and AVP rhythms were phase-advanced in T-CR mice, the PER2 rhythm showed an increased amplitude. CLOCK was expressed constitutively in AL mice while in T-CR it was significantly reduced, especially after feeding time. A light pulse produced a delayed increase in PER1 and a larger increase in PER2 expression in the SCN of T-CR mice than in AL animals. In addition, light exposure triggered an increase in AVP-ir cells in both AL and T-CR mice, and also of CLOCK expression but in T-CR mice only. The circadian changes in clock and clock-controlled proteins and their acute responses to light in the SCN of T-CR mice demonstrate that metabolic cues induced by a calorie restriction modulate the translational regulation of the SCN clock.