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Food-anticipatory activity (FAA) and especially the food-entrained oscillator (FEO) have driven many scientists to seek their mechanisms and locations. Starting our research on FAA we, possibly like many other scientists, were convinced that clock genes held the key to the location and the underlying mechanisms for FAA. In this review, which is aimed especially at discussing the contribution of the peripheral oscillators, we have put together the accumulating evidence that the clock gene machinery as we know it today is not sufficient to explain food entrainment. We discuss the contribution of three types of oscillating processes: (i) within the suprachiasmatic nucleus (SCN), neurons capable of maintaining a 24-h oscillation in electrical activity driven by a set of clock genes; (ii) oscillations in metabolic genes and clock genes in other parts of the brain and in peripheral organs driven by the SCN or by food, which damp out after a few cycles; (iii) an FEO which, we propose, is a system built up of different oscillatory processes and consisting of an as-yet-unidentified network of central and peripheral structures. In view of the evidence that clock genes and metabolic oscillations are not essential for the persistence of FAA we propose that food entrainment is initiated by a repeated metabolic state of scarcity that drives an oscillating network of brain nuclei in interaction with peripheral oscillators. This complex may constitute the proposed FEO and is distributed in our peripheral organs as well as within the central nervous system. [ABSTRACT FROM AUTHOR]

Restricted feeding schedules (RFS) are a potent Zeitgeber that uncouples daily metabolic and clock gene oscillations in peripheral tissues from the suprachiasmatic nucleus (SCN), which remains entrained to the light–dark cycle. Under RFS, animals develop food anticipatory activity (FAA), characterized by arousal and increased locomotion. Food availability in nature is not precise, which suggests that animals need to adjust their food-associated activity on a daily basis. This study explored the capacity of rats to adjust to variable and unpredictable feeding schedules. Rats were exposed either to RFS with fixed daily meal (RF) or to a variable meal time (VAR) during the light phase. RF and VAR rats exhibited daily metabolic oscillations driven by the last meal event; however, VAR rats were not able to show a robust adjustment in the anticipating corticosterone peak. VAR rats were unable to exhibit FAA but exhibited a daily activation pattern in phase with the previous meal. In both groups the dorsomedial nucleus of the hypothalamus and arcuate nucleus, involved in energy balance, exhibited increased c-Fos expression 24 h after the last meal, while only RF rats exhibited low c-Fos expression in the SCN. Data show that metabolic and behavioural food-entrained rhythms can be reset on a daily basis; the two conditions elicit a similar hypothalamic response, while only the SCN is inhibited in rats exhibiting anticipatory activity. The variable feeding strategy uncovered a rapid (24-h basis) resetting mechanism for metabolism and general behaviour. [ABSTRACT FROM AUTHOR]

Food entrainment of clock genes in peripheral tissues and anticipatory response in the liver of rats maintained under a restricted feeding schedule have suggested that the liver may be a relevant element for a food entrained oscillator (FEO). Recent data suggest that mechanisms underlying food-entrainment for metabolic and behavioral or locomotor food anticipatory activity may depend on different regulatory systems. In a previous study we reported that a dysfunctional liver does not prevent animals from exhibiting behavioral anticipatory activity associated with restricted feeding schedules (RFS). The present study aimed to determine whether in CCl4 cirrhotic rats metabolic parameters are entrained to RFS. Chronic CCl4 treated cirrhotic rats and oil treated controls were entrained to RFS. After 2 weeks, rats were sacrificed 2 and 0?h before and 2 and 4?h after mealtime. Serum glucose and free fatty acids were determined as well as liver glycogen. Both groups exhibited a similar entrained pattern in the three parameters. Thus we conclude that anatomical and functional alterations produced by chronic administration of CCl4 do not interfere with entrainment of metabolic parameters to RFS and point out the relevance of other mechanisms independent of the liver to drive peripheral food entrained rhythms. [ABSTRACT FROM AUTHOR]