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In the newborn rabbit, the light entrainable circadian system is immature and once a day nursing provides the primary timing cue for entrainment. In advance of the mother's arrival, pups display food anticipatory activity (FAA), and metabolic and physiological parameters are synchronized to this daily event. Central structures in the brain are also entrained as indicated by expression of Fos and Per1 proteins, GFAP, a glial marker, and cytochrome oxidase activity. Under fasting conditions, several of these rhythmic parameters persist in the periphery and brain, including rhythms in the olfactory bulb (OB). Here we provide an overview of these physiological and neurobiological changes and focus on three issues, just beginning to be examined in the rabbit. First, we review evidence supporting roles for the organum vasculosum of lamina terminalis (OVLT) and median preoptic nucleus (MnPO) in homeostasis of fluid ingestion and the neural basis of arousal, the latter which also includes the role of the orexigenic system. Second, since FAA in association with the daily visit of the mother is an example of conditioned learning, we review evidence for changes in the corticolimbic system and identified nuclei in the amygdala and extended amygdala as part of the neural substrate responsible for FAA. Third, we review recent evidence supporting the role of oxytocinergic cells of the paraventricular hypothalamic nucleus (PVN) as a link to the autonomic system that underlies physiological events, which occur in preparation for the upcoming next daily meal. We conclude that the rabbit model has contributed to an overall understanding of food entrainment.

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In mammals, the suprachiasmatic nucleus (SCN), the master circadian clock, is mainly synchronized to the environmental light/dark cycle. SCN oscillations are maintained by a molecular clockwork in which certain genes, Period 1-2, Cry1-2, Bmal1, and Clock, are rhythmically expressed. Disruption of these genes leads to a malfunctioning clockwork and behavioral and physiological rhythms are altered. In addition to synchronization of circadian rhythms by light, when subjects are exposed to food for a few hours daily, behavioral and physiological rhythms are entrained to anticipate mealtime, even in the absence of the SCN. The presence of anticipatory rhythms synchronized by food suggests the existence of an SCN-independent circadian pacemaker that might be dependent on clock genes. Interestingly, rabbit pups, unable to perceive light, suckle milk once a day, which entrains behavioral rhythms to anticipate nursing time. Mutations of clock genes, singly or in combination, affect diverse rhythms in brain activity and physiological processes, but anticipatory behavior and physiology to feeding time remains attenuated or unaffected. It had been suggested that compensatory upregulation of paralogs or subtypes genes, or even non-transcriptional mechanisms, are able to maintain circadian oscillations entrained to mealtime. In the present mini-review, we evaluate the current state of the role played by clock genes in meal anticipation and provide evidence for rabbit pups as a natural model of food-anticipatory circadian behavior.

RESUMO

Travelling across several time zones requires a fast adjustment of the circadian system and the differential adjustment speeds of organs and systems results in what is commonly referred as jet lag. During this transitory state of circadian disruption, individuals feel discomfort, appetite loss, fatigue, disturbed sleep and deficient performance of multiple tasks. We have demonstrated that after a 6-h phase advance of the light-dark cycle (LD) scheduled food in phase with the new night onset can speed up re-entrainment. In this study, we explored the possible mechanisms underlying the fast re-entrainment due to the feeding schedule. We focused on first- and second-order structures that provide metabolic information to the suprachiasmatic nucleus (SCN). We compared (i) control rats without change in LD cycle; (ii) rats exposed to a 6-h phase advance of the LD cycle with food ad libitum; and (iii) rats exposed to the 6-h phase advance combined with food access in phase with the new night. We found an immediate synchronizing effect of food on stomach distention and on c-Fos expression in the nucleus of the solitary tract, arcuate nucleus of the hypothalamus, dorsomedial hypothalamic nucleus and paraventricular nucleus. These observations indicate that in a model of jet lag, scheduled feeding can favour an immediate shift in first- and second-order relays to the SCN and that by keeping feeding schedules coupled to the new night, a fast re-entrainment may be achieved by shifting peripheral and extra-SCN oscillations.

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RESUMO

Resumen: Esta revisión tiene como objetivo presentar evidencias obtenidas mediante observaciones clínicas y modelos animales que señalan la relevancia que tiene el horario de alimentación sobre el metabolismo y el mantenimiento del peso corporal. Hallazgos recientes han puesto en evidencia que la misma cantidad de alimento ingerida durante el día o la noche afecta diferencialmente el metabolismo, lo que determina una diferencia significativa en el desarrollo del sobrepeso y la obesidad. Este conocimiento se fundamenta en el estudio del sistema circadiano, regido por el reloj biológico del hipotálamo anterior, que le transmite tiempos a todas las funciones del cuerpo, incluyendo aquellas para el gasto y el ahorro de energía. A pesar de que estos ciclos circadianos están normalmente regulados por los cambios de iluminación resultantes de la alternancia del día y la noche, los cambios metabólicos que resultan de una comida han mostrado también ser señales de tiempo que modifican el orden temporal de algunos sistemas y grupos celulares. De ello se desprende que para que el sistema circadiano funcione sincronizado, las horas de alimentación deben coincidir con los ciclos dictados por el reloj biológico. De tal manera, comer durante las horas normalmente asignadas al reposo lleva a la pérdida de coordinación de los ritmos circadianos metabólicos con respecto al reloj biológico. Esta desincronización sucede a diferentes niveles, tanto entre las células de los tejidos como en una misma célula a nivel molecular. En esta revisión se enfatizarán los efectos adversos de las comidas por la noche sobre el metabolismo energético, además se presentarán resultados recientes que describen los cambios circadianos y metabólicos a diversos niveles de regulación.

Abstract: The present review aims to present evidence obtained in clinical surveys and experimental studies that point out the relevance of meal schedules on metabolism and body weight. Recent findings indicate that in spite of ingesting equivalent amounts, food ingestion during the day or during the night can have completely different effects on metabolism determining bodyweight gain and propensity to obesity. Such findings find support in studies of the circadian rhythms, driven by a biological clock located in the anterior hypothalamus, which transmits temporal signals to the body including functions for energy balance. Circadian cycles are normally driven by the alternation of the day- night luminosity cycles, however metabolic changes resulting from food have proven to be powerful temporal signals capable of modifying de temporal order in tissues and cells. Considering the power of food elicited signals, the feeding schedule must coincide with the timing signals driven by the biological clock. Thus eating during the hours normally assigned for sleep and rest leads to a loss of coordination between metabolic rhythms and the biological clock. This circadian disruption occurs at different levels, among cells in a specific tissue as well as in the molecular processes in cells. The aim of this review is to emphasize the adverse effects that meals during the night can exhert on metabolism, we provide evidence about circadian and metabolic alterations at different regulatory levels.

RESUMO

Scheduled and restricted access to a palatable snack, i.e. chocolate, elicits a brief and strong anticipatory activation and entrains brain areas related with reward and motivation. This behavioral and neuronal activation persists for more than 7days when this protocol is interrupted, suggesting the participation of a time-keeping system. The process that initiates this anticipation may provide a further understanding of the time-keeping system underlying palatable food entrainment. The aim of this study was to analyze how this entraining protocol starts and to dissect neuronal structures that initiate a chocolate-entrained activation. We assessed the development of anticipation of 5g of chocolate during the first 8days of the entrainment protocol. General activity of control and chocolate-entrained rats was continuously monitored with movement sensors. Moreover, motivation to obtain the chocolate was assessed by measuring approaches and interaction responses toward a wire-mesh box containing chocolate. Neuronal activation was determined with c-Fos in reward-related brain areas. We report a progressive increase in the interaction with a box to obtain chocolate parallel to a progressive neuronal activation. A significant anticipatory activation was observed in the prefrontal cortex on day 3 of entrainment and in the nucleus accumbens on day 5, while the arcuate nucleus and pyriform cortex reached significant activation on day 8. The gradual response observed with this protocol indicates that anticipation of a rewarding food requires repetitive and predictable experiences in order to acquire a temporal estimation. We also confirm that anticipation of palatable food involves diverse brain regions.

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