Circadian clocks: setting time by food.

In mammals, daily rhythms in behaviour and physiology are driven by a circadian timing system comprised, in a hierarchical way, of a master pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus and of peripheral oscillators in most body cells. At the molecular level, in both the SCN and peripheral oscillators, the circadian clock mechanism is built from interconnected feedback loops in gene expression that operate in a cell-autonomous and self-sustained fashion. The SCN clock is mainly entrained by light/dark cycles. By contrast, peripheral oscillators can be strongly affected by daily feeding cycles, which have little effect on the phase of the SCN. However, when feeding schedules are coupled with a caloric restriction, behavioural and physiological circadian rhythms and gene expression in the SCN are shifted and/or entrained to meal-time. Moreover, the reward and motivational value of food can also be a potent synchroniser for the SCN clock. This suggests that energy metabolism and motivational properties of food can influence the clock mechanism of the SCN. Food-related cues may entrain clock genes of the SCN with a direct effect, or be mediated indirectly by another neural or peripheral site. In addition, there may be one or more oscillator sites that would play an integral role as a food-entrained oscillator (FEO), responsible for anticipation of meal-time. The site housing, or the network underlying, this putative FEO is still unknown. The aim of this review is to summarise our current knowledge of the central and peripheral circadian clocks and how they can be entrained by feeding at the physiological and molecular levels.