Restricted feeding schedules alter the circadian rhythms of serum insulin and gastric inhibitory polypeptide

Insulin and gastric inhibitory polypeptide (GIP) have a circadian rhythm of secretion that is altered by various feeding schedules. We acclimated rats over 3 weeks to one of 6 different feeding schedules. They were then killed at intervals over one feeding cycle. Blood was collected, and their stomachs were weighed. Hormones in the serum were measured by radioimmunoassay. When highest and lowest measured concentrations were compared in ad libitum fed rats, insulin more than doubled (445 +/- 50 to 993 +/- 180 pg/ml) and GIP more than tripled (682 +/- 108 to 1964 +/- 145 pg/ml) during a 24-h period. With restricted schedules, concentrations correlated with the feeding schedule, not the light-dark cycle. Hormone levels rose higher during feeding and fell lower with fasting than in ad lib fed rats. For example, GIP in one study fluctuated from 468 +/- 22 to 6433 +/- 432 pg/ml. In another example, insulin ranged from 30 +/- 5 to 2259 +/- 406 pg/ml during a 24-h period. However, insulin did not always correlate well with stomach weight. Circadian rhythms occurred for insulin with all feeding schedules and for GIP with all schedules except fasted rats. This finding implies an endogenous insulin rhythm, whereas food intake controls GIP secretion. Thus, disruption of normal circadian cycles of feeding may yield misleading information about gut hormone secretion.     

Scheduled feeding versus the light-dark cycle on the rhythms of circulating tryptophan, serotonin and N-acetylserotonin in rats

Both the environmental light-dark cycle and scheduled feeding can act as entrainers of biological rhythms. The present study investigated the relative potency of these two environmental cues in entraining the rhythms of circulating tryptophan (TRP), serotonin (5HT) and N-acetylserotonin (NAS). Four groups of rats were subjected for one month to an identical light-dark cycle of 14 h light and 10 h dark with food availability restricted to the 3 h period beginning 2 h after onset of light or onset of darkness. Two groups of animals were food deprived on the day of experiment. The 24 h rhythms of serum TRP, 5HT and NAS were determined. Serum TRP showed a sharp increase after food presentation and declined gradually to a trough just before feeding. Withholding food on the day of experiment abolished this increase. The trough of serum 5HT occurred just before feeding, increased gradually after feeding and peaked 10-13 h afterwards. Serum NAS levels, however, demonstrated an anticipatory rise before feeding, which peaked during feeding and declined to a trough 8 h afterwards. Unlike TRP, withholding food had no effect on either the 5HT or the NAS rhythm. These results indicated that feeding schedule was the common and stronger entrainer for the rhythms of serum TRP, 5HT and NAS. However, each indole had a different rhythm pattern in relation to the feeding schedule which could not be explained by a simple precursor-product relationship.     

Reanalysis of Filter-Feeding Behavior of Caddis Fly (Brachycentrus) Larvae Reveals Masking and Circadian Rhythmicity

Data published on the subjectively determined presence or absence of circadian periodicity in feeding of Brachycentrus occidentalis Banks, an aquatic insect belonging to the order Trichoptera, were reanalyzed by statistical methods based on the cosine model. The 4h data for 5 days of synchronized environmental conditions followed by 5 days of constant conditions (using original values and purified values after removal of an 8h component attributed to the feeding schedule) were quantified for rhythm characteristics by the least-squares fit of cosines. A circadian rhythm was highly significant during synchronized conditions (light-dark and cycling water temperature) and in continuous light when water temperature continued to cycle. A circadian rhythm in the percentage of larvae feeding during continuous light and constant water temperature, which had not been observed by visual inspection in the original data, was detected in the unmasked data with a “free-running” period not overlapping 24.0h (95% confidence limits from 18.95h to 21.66h). Effects of masking brought about by manually feeding the larvae every 8h were statistically significant under both synchronized and constant environmental conditions. (Chronobiology International, 15(6), 595-606, 1998)     

SYNCHRONIZATION TO LIGHT AND RESTRICTED-FEEDING SCHEDULES OF BEHAVIORAL AND HUMORAL DAILY RHYTHMS IN GILTHEAD SEA BREAM (SPARUS AURATA)

Food is not continuously available in the wild, and so most animals show a wide variety of circadian rhythms that can be entrained to feeding time. The aim of this research was to evaluate the effect of time-restricted feeding on the daily rhythms of gilthead sea bream, with food being provided during the day or night under a 12:12?h light-dark (LD) cycle or constant light (LL) conditions. Self-feeding and locomotor activity, as well as daily rhythms of cortisol, glucose, and melatonin, were evaluated. Fish synchronized their feeding behavior to the feeding phase, so that in LD they displayed 78% nocturnal feeding activity under night-feeding and 81% diurnal feeding activity under day-feeding, while under LL-feeding they displayed 72% of their daily activity during the 12?h feeding phase. In contrast, locomotor activity was mostly diurnal (66–71%), regardless of the feeding schedule, and it became arrhythmic under LL. Cortisol showed daily rhythms that peaked at different times, depending on the light and feeding schedule: one peak several hours before feeding under day-feeding and night-feeding, and two peaks under LL-feeding. Glucose displayed low-amplitude variations, with no daily rhythms being detected. Melatonin, however, showed a nocturnal rhythm, regardless of the feeding schedule, while the rhythm became attenuated under LL. Taken together, these results highlight the role of feeding on endocrine and metabolic rhythms, suggesting that feeding behavior should be considered when studying these variables. (Author correspondence: jflopez@um.es)     

Entrainment of Circadian Wheel-Running Rhythms of the Northern Brown Bandicoot, Isoodon macrourus, by Daily Restricted Feeding Schedules

Northern brown bandicoots (Isoodon macrourus) were subjected to restricted feeding for 3 h in the middle of the light period of a 14: 10 light/dark cycle and immediately following this in constant dark. When feeding was restricted to the middle of the light period of the light/dark cycle, all bandicoots maintained a nocturnal activity rhythm. In addition to the nocturnal rhythm, a few bandicoots showed meal-anticipatory activity during the light period. In bandicoots that did not show meal-anticipatory activity, diurnal activity was sometimes evident either during or shortly after the daily meal time. The observation of meal-anticipatory activity in some bandicoots suggests that this species may have a mechanism separate from the light-entrainable mechanism that allows the daily anticipation of periodically available food sources. In the next stage of the experiment, which was in constant dark, the meal was presented at the same time of day as it had been in the previous stage. In all bandicoots, the previously light-entrained component of activity free-ran and was eventually affected by the restricted feeding schedule to some degree. Bandicoots showed weak entrainment and relative coordination, suggesting that restricted feeding is a weak zeitgeber in this species. Evidence also suggesting that two separate but coupled pacemakers control the activity rhythms of the bandicoot was that (a) bandicoots simultaneously showed free-running light-entrainable rhythms and meal-entrained anticipatory rhythms; (b) in several bandicoots, the light-entrainable rhythm was phase advanced when it free-ran through the meal time; and (c) in one bandicoot, meal-entrained anticipatory activity was forced away from the meal time when the previously light-entrained component of activity free-ran through it.     

The comparison between circadian oscillators in mouse liver and pituitary gland reveals different integration of feeding and light schedules

The mammalian circadian system is composed of multiple peripheral clocks that are synchronized by a central pacemaker in the suprachiasmatic nuclei of the hypothalamus. This system keeps track of the external world rhythms through entrainment by various time cues, such as the light-dark cycle and the feeding schedule. Alterations of photoperiod and meal time modulate the phase coupling between central and peripheral oscillators. In this study, we used real-time quantitative PCR to assess circadian clock gene expression in the liver and pituitary gland from mice raised under various photoperiods, or under a temporal restricted feeding protocol. Our results revealed unexpected differences between both organs. Whereas the liver oscillator always tracked meal time, the pituitary circadian clockwork showed an intermediate response, in between entrainment by the light regimen and the feeding-fasting rhythm. The same composite response was also observed in the pituitary gland from adrenalectomized mice under daytime restricted feeding, suggesting that circulating glucocorticoids do not inhibit full entrainment of the pituitary clockwork by meal time. Altogether our results reveal further aspects in the complexity of phase entrainment in the circadian system, and suggest that the pituitary may host oscillators able to integrate multiple time cues.     

Circadian rhythms of body temperature and liver function in fed and food-deprived goats

Daily rhythms of body core temperature and liver function were recorded in goats maintained under various schedules of lighting and feeding. Concentration of urea in the blood was used as an index of digestion-driven hepatic activity, whereas concentration of cholesterol served as an index of autonomous hepatic activity. Body temperature exhibited robust circadian rhythmicity in the presence and absence of a light-dark cycle and/or a feeding regime. The rhythm was more responsive to shifts in feeding time than to shifts in the light-dark cycle. Urea concentration in the blood exhibited daily rhythmicity only in the presence of a daily feeding regime and, therefore, was driven by ingestive and digestive processes. The rhythm of cholesterol concentration persisted in the presence or absence of a light-dark cycle and/or a feeding regime, except when the feeding time was shifted under constant light. However, the cholesterol rhythm did not respond either to shifts in the light-dark cycle or, more importantly, to shifts in feeding time. Thus, based on this index of hepatic function, the liver cannot be identified as the site of the putative food-entrainable pacemaker.     

Effects of feeding schedules on diurnal periodicity of Leucocytozoon smithi gametocytes in the peripheral blood of domestic turkeys

Eighteen domestic turkeys naturally infected with Leucocytozoon smithi Laveran & Lucet were maintained on restricted feeding schedules under conditions of either continuous light or natural light (light 13 h:darkness 11 h) photoperiods. Peripheral gametocyte numbers of L. smithi in all turkeys were determined every 2 h over a 36-h period. Peripheral gametocyte numbers of turkeys maintained under continuous light and restricted to either a 10-h feeding period (9:30 p.m. to 7:30 a.m.) once a day or a 2-h feeding period twice a day (7:30 a.m. to 9:30 p.m. and 7:30 p.m. to 9:30 p.m.) increased at or near the time of feed availability. Under natural photoperiod, gametocyte periodicity was not affected by restricting feed availability to the dark phase of the light-dark cycle. Mean parasite numbers were highest during the light phase when feed was not available, and lowest during the dark period when feed was accessible.     

Effects of feeding cycles on circadian rhythms in squirrel monkeys

Squirrel monkeys (Saimiri sciureus) were housed singly in cages equipped with a tree for climbing to measure locomotor activity, and with a movable food cup that could be arrested automatically. The animals were kept in continuous dim illumination (LL), twice interrupted by several weeks of entrainment by a light-dark (LD) 12:12 cycle. Apart from three control sections in which the food cups were unlocked continuously (ad libitum feeding), food was accessible for 3 hr per day only, with interfeeding intervals varying from 23 to 26 hr (periodic restricted feeding, or RF). During LD entrainment, the imposition of an RF schedule resulted in anticipatory behaviors, represented by increased tugs at the food cup and a pause in locomotor activity preceding the feeding time. In LL, the animals showed free-running circadian rhythms of locomotor and "feeding" activity that nearly always persisted when ad libitum feeding was replaced by RF. The period (tau) of the free-running rhythm was slightly modulated in relation to the varying interfeeding intervals (T), but entrainment was never achieved except in one test with an animal whose tau was very close to T. It is concluded that periodic availability of food represents an extremely weak zeitgeber, if any, for the circadian pacemaker of squirrel monkeys.     

Circadian rhythms in honeybees: entrainment by feeding cycles

ABSTRACT. Colonies of the South African honeybee race Apis mellifera capensis (Escholtz) were maintained under constant conditions of illumination (200 lux), temperature (25±lC) and relative humidity (65±3%). Activity was measured at the hive entrance. After ad libitum feeding for at least 5 days, food was presented for only 2 h/day either for 1 week (series 1) or for 2 weeks (series 2). In the last part of each experiment, food was again available all the time. Colonies which showed free-running circadian activity rhythms (with periods ranging from 22.6 to 24.8 h) during ad libitum feeding were submitted to feeding cycles with inter-feeding intervals (T) of 22, 23, 24 and 25 h. In most of these experiments the rhythms were synchronized by the feeding schedule, resulting in a stable phase-angle difference between onset of activity and onset of food availability. The duration of this anticipatory activity was positively correlated with T. When ad libitum feeding was resumed, the period of the rhythm induced by the feeding schedule persisted for a few days. Thereafter, the rhythm was free-running again with a period close to that observed in the first part of the experiment. The conclusion is drawn that, under the influence of periodic feeding, the activity of honeybee colonies has the characteristics of an entrained circadian system.     

The effects of food presentation at regular or irregular times on the development of activity-based anorexia in rats

Activity-based anorexia occurs when food availability is restricted to 1 h of the day and a wheel is freely available to the rest of the time. Under such conditions rats run excessively and stop eating even during periods in which food is available. A defining characteristic of the excessive activity is that there is a peak of running in the anticipation of food availability. The present study was designed to test whether the occurrence of the food period at different times of the light phase of the light-dark cycle (from 08:00 to 20:00 h) could impede or postpone the normal development of activity anorexia. We compared the effect of presenting the food at a fixed time of the light period with presenting it on a variable schedule. Far from impeding or postponing the development of activity-based anorexia, presenting food at irregular times resulted in a pronounced body-weight loss, a low food intake and an increase in locomotor activity. Animals ran excessively, with a peak at the start of the dark period, and again when lights were turned on in the experimental room (running in the anticipation of food). Both fixed and variable schedules of food availability resulted in the development of activity-based anorexia in rats.     

Evidence for circadian rhythmicity in guanyl cyclase of the rat intestinal epithelial cell.

The activity of the enzyme, guanyl cyclase, associated with the rat intestinal brush border membrane, has an endogenous circadian rhythm which is observed in the absence of oral intermittent feeding and of a dark period. This rhythm is cued by the feeding schedule but is essentially unaffected by a light-dark cycle.     

Feeding time synchronizes clock gene rhythmic expression in brain and liver of goldfish (Carassius auratus)

Little is known about the feeding time dependence of clock gene expression in fish. The aim of the present study was to investigate whether a scheduled feeding time can entrain the rhythmic expression of several clock genes (period and cryptocrome) in the brain and liver of a teleost, the goldfish. Fish maintained under continuous light (LL) conditions were divided into 3 groups. Two groups were fed daily at 1000 h and 2200 h, respectively, and the third group was subjected to a random schedule regime. After 30 days, the fishes under 24-h food deprivation were sacrificed through a 24-h cycle, and clock gene expression in the optic tectum, hypothalamus, and liver was quantified by real-time PCR. The findings pointed to differences between the central and peripheral tissues studied. In the absence of a light-dark cycle (constant light), a scheduled feeding regime was necessary and sufficient to maintain both the rhythmic expression of several clock genes in the optic tectum and hypothalamus, as well as daily rhythms in locomotor activity. In contrast, neither locomotor activity nor clock gene expression in brain tissues was synchronized in randomly fed fish. However, in the liver, most of the clock genes studied presented significant daily rhythms in phase (related to the time of the last meal) in all 3 experimental groups, suggesting that the daily rhythm of clock genes in this organ only depends on the last meal time. The data suggest that, as in mammals, the smooth running of the food entrainable oscillator (FEO) in fish involves the rhythmic expression of several clock genes (Per1 and Cry3) in the central and peripheral structures. The results also indicate that the food anticipatory activity (FAA) in goldfish is not only the result of rhythmic clock gene expression in the liver because rhythmic clock gene expression was observed in randomly fed fishes, while FAA was not observed.     

Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats

The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b)) rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b) rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b) rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.     

Diurnal changes in intestinal apolipoprotein A-IV and its relation to food intake and corticosterone in rats

To further investigate the role of intestinal aplipoprotein A-IV (apo A-IV) in the management of daily food intake, we examined the diurnal patterns in apo A-IV gene and protein expression in freely feeding (FF) and food-restricted (FR; food provided 4 h daily for 4 wk) rats that were killed at 3-h intervals throughout the 24-h diurnal cycle. In FF rats, the intestinal apo A-IV mRNA and protein levels showed a circadian rhythm concomitant with the feeding pattern. The daily pattern of fluctuation of apo A-IV, however, was altered in FR rats, which had a marked increase in intestinal apo A-IV levels during the 4-h feeding period of light phase. In both FF and FR rats, increased plasma corticosterone (Cort) levels temporally coincided with the increasing phase of intestinal apo A-IV mRNA and protein expression. Depletion of Cort by adrenalectomy abolished the diurnal rhythm by decreasing the apo A-IV expression during the dark period but did not change the feeding rhythm. Exposure of adrenalectomized rats to consistent Cort level (50-mg continuous release Cort pellet) resulted in fixed apo A-IV levels throughout the day. These results indicate that intestinal apo A-IV exhibits a diurnal rhythm, which can be regulated by endogenous Cort independently of the light-dark cue. The fact that intestinal apo A-IV levels were consistent with the food intake during the normal diurnal cycle as well as during the cycle of 4-h feeding each day suggests that intestinal apo A-IV is involved in the regulation of daily food intake.     

Food- and light-entrainable oscillators control feeding and locomotor activity rhythms, respectively, in the Japanese catfish, Plotosus japonicus

Feeding and locomotor activities of the Japanese catfish Plotosus japonicus under solitary condition were recorded to identify mechanisms controlling these behaviours. In the absence of food, the catfish showed nocturnal locomotor activity, but no feeding activity. Under ad libitum food conditions, both feeding and locomotor activities occurred during the dark period and were synchronized with light/dark (LD) cycles. Feeding activity lasted for 11–24 days when food was stopped after ad libitum food availability. Restricted food during the light phase produced both food-anticipatory and light-entrainable feeding activity. Furthermore, this condition produced weak food-anticipatory and light-entrainable locomotor activity. Under the light/light (LL) condition, restricted food produced food-anticipatory feeding and locomotor activities, suggesting that a food-entrainable oscillator controls both feeding and locomotor activities. However, under the LL condition, light-entrainable feeding and locomotor activities were not observed, suggesting that a light-entrainable oscillator controls both feeding and locomotor activities. During a restricted food schedule, LD cycle shifts resulted in disrupted synchronization of feeding activity onset in three of the four fish, but one fish showed synchronized feeding activity. These results suggest that the food- and the light-entrainable oscillator may control feeding and locomotor activities, respectively.     

Effect of restricted feeding schedule on seasonal shifting of daily demand-feeding pattern and food anticipatory activity in European sea bass (Dicentrarchus labrax L.)

The effect of restricted feeding schedule was investigated on the seasonal shifting of daily demand-feeding pattern and food anticipatory activity in European sea bass (Dicentrarchus labrax) held under natural environmental conditions in an outdoor laboratory. To that end, demand-feeding behavior was continuously monitored for approximately one year in four groups of 15 fish each exposed to natural fluctuations of water temperature (from 13.2 degrees C to 27.4 degrees C) and photophase (from 9.5 h to 14.5 h of light). When the animals were subjected to a time-restricted feeding schedule, the demand-feeding rhythm rapidly synchronized to the three periods of food availability: the first meal (FM) from 08:00 to 09:00 h, the second meal (SM) from 16:00 to 17:00 h, and the third meal (TM) from 00:00 to 01:00 h. The occurrence of demand-feeding activity into the three periods of food availability displayed a double seasonal shift: fish that self-fed mostly during the daytime periods of feeding availability (FM and SM) in summer and autumn changed to nocturnal feeding (TM) from December to April, returning to diurnal preferences in April. Food-demands appeared to be predominantly associated with feed availability, reaching its maximum levels during the hours of reward. In addition, feeding anticipatory activity (FAA) was observed. A relationship was detected between the duration of FAA and feeding-time, with shortest FAA (30-60 min) when mealtime occurred just after sunrise (FM) or sunset (TM). These findings demonstrate the ability of sea bass to self-feed under time-restricted schedules, and show a seasonal-phase inversion in demand-feeding activity in spite of the restrictions in their feeding availability. Sea bass can use external signals as reference to anticipate the time of feed availability. This information may be useful for designing new feeding strategies for European sea bass fish farming.     

Rapid reset of the corticosterone rhythm by food presentation in rats under acircadian restricted feeding schedule

Corticosterone levels were determined in the 7-week-old male rat maintained under different feeding and lighting schedules. At 4 weeks of age, the animals were kept either under a natural photoperiod (LD) or were subjected to continuous illumination (LL). Access to food was either ad libitum or restricted to an 8 hr span per 24 hr (circadian) or 32 hr (acircadian).

The food signal seemed able to synchronize the corticosterone rhythm to its own circadian periodicity, irrespective of the lighting regimen. No synchronization was observed in serially sampled LL or LD rats under an acircadian feeding schedule. Instead, the group acrophase appeared 24 hr subsequent to food presentation. Regarding individual patterns, many rats showed an acrophase or a peak also at that time. We speculate that an endogenous circadian mechanism was reset by the food signal, whenever it appeared.     

The homeostatic feeding response to fasting is under chronostatic control

ABSTRACT

Eating behavior is controlled by the energy needs of the organism. The need to provide a constant supply of energy to tissues is a homeostatic drive that adjusts feeding behavior to the energetic condition of the organism. On the other hand, food intake also shows a circadian variation synchronized to the light-dark cycle and food availability. Thus, feeding is subjected to both homeostatic and circadian regulation mechanisms that determine the amount and timing of spontaneous food intake in normal conditions. In the present study we contrasted the influence of the homeostatic versus the chronostatic mechanisms on food intake in normal conditions and in response to fasting. A group of rats was subjected to food deprivation under two different temporal schemes. A constant-length 24-h food deprivation started at different times of day resulted in an increased compensatory intake. This compensatory response showed a circadian variation that resembled the rhythm of intake in non-deprived animals. When subjected to fasting periods of increasing length (24–66 h), the amount of compensatory feeding varied according to the time of day in which food was made available, being significantly less when the fast ended in the middle of the light phase or beginning of the dark phase. These oscillatory changes did not have a correlation with variations in the level of glucose or β-hydroxybutyrate in the blood. The results suggest that the mechanism of homeostatic compensation is modulated chronostatically, presumably as part of the alternation of catabolic and anabolic states matching the daily cycles of activity.