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Robust food anticipatory activity in BMAL1-deficient mice.

Pendergast JS, Nakamura W, Friday RC, Hatanaka F, Takumi T, Yamazaki S - PLoS ONE (2009)

Bottom Line: We found that BMAL1-deficient mice displayed FAA during restricted feeding in 12hr light:12hr dark (12L:12D) and 18L:6D lighting cycles, but distinct activity during food deprivation was observed only in 18L:6D.While BMAL1-deficient mice also exhibited robust FAA during restricted feeding in constant darkness, mice were hyperactive during food deprivation so it was not clear that FAA consistently occurred at the time of previously scheduled food availability.Furthermore, the expression of FAA may be possible without a circadian oscillator that depends on BMAL1.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.

ABSTRACT
Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Even though nocturnal rodents prefer to forage at night, daytime food anticipatory activity (FAA) is observed prior to short meals presented at a scheduled time of day. Under this restricted feeding regimen, rodents exhibit two distinct bouts of activity, a nocturnal activity rhythm that is entrained to the light-dark cycle and controlled by the master clock in the suprachiasmatic nuclei (SCN) and a daytime bout of activity that is phase-locked to mealtime. FAA also occurs during food deprivation, suggesting that a food-entrainable oscillator (FEO) keeps time in the absence of scheduled feeding. Previous studies have demonstrated that the FEO is anatomically distinct from the SCN and that FAA is observed in mice lacking some circadian genes essential for timekeeping in the SCN. In the current study, we optimized the conditions for examining FAA during restricted feeding and food deprivation in mice lacking functional BMAL1, which is critical for circadian rhythm generation in the SCN. We found that BMAL1-deficient mice displayed FAA during restricted feeding in 12hr light:12hr dark (12L:12D) and 18L:6D lighting cycles, but distinct activity during food deprivation was observed only in 18L:6D. While BMAL1-deficient mice also exhibited robust FAA during restricted feeding in constant darkness, mice were hyperactive during food deprivation so it was not clear that FAA consistently occurred at the time of previously scheduled food availability. Taken together, our findings suggest that optimization of experimental conditions such as photoperiod may be necessary to visualize FAA in genetically modified mice. Furthermore, the expression of FAA may be possible without a circadian oscillator that depends on BMAL1.

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The timing of food deprivation affects food anticipatory activity (FAA).Diagrams of restricted feeding protocols when mice are food deprived starting at ZT3 (A) or ZT12 (C). Wildtype C57BL/6J mice were fed ad libitum and then food availability was gradually reduced (RF) from 8 hrs/day to 6 hrs/day. Then mice were fed 4 hrs/day (from ZT6 to ZT10) for at least 9 days and then provided food ad libitum for 6 days. The time when food was available is indicated by gray shading in A and C. On the seventh day of ad libitum feeding, food was removed at either ZT3 (A, B) or ZT 12 (C, D). Food was replaced 48 hrs later. Group average activity profiles for mice that began fasting at ZT3 (B; n = 4) or ZT12 (D; n = 5) were generated by averaging the number of wheel revolutions per 10-minute bin (black line) and were plotted relative to the light-dark cycle where ZT0 is the time of lights on and ZT12 is lights off. The SEM, which represents the variability among mice, is shown in dark gray shading. The time of previously scheduled food availability is indicated by dotted lines in the activity profiles. The light-dark cycle is indicated by the white and black bars, respectively.
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pone-0004860-g001: The timing of food deprivation affects food anticipatory activity (FAA).Diagrams of restricted feeding protocols when mice are food deprived starting at ZT3 (A) or ZT12 (C). Wildtype C57BL/6J mice were fed ad libitum and then food availability was gradually reduced (RF) from 8 hrs/day to 6 hrs/day. Then mice were fed 4 hrs/day (from ZT6 to ZT10) for at least 9 days and then provided food ad libitum for 6 days. The time when food was available is indicated by gray shading in A and C. On the seventh day of ad libitum feeding, food was removed at either ZT3 (A, B) or ZT 12 (C, D). Food was replaced 48 hrs later. Group average activity profiles for mice that began fasting at ZT3 (B; n = 4) or ZT12 (D; n = 5) were generated by averaging the number of wheel revolutions per 10-minute bin (black line) and were plotted relative to the light-dark cycle where ZT0 is the time of lights on and ZT12 is lights off. The SEM, which represents the variability among mice, is shown in dark gray shading. The time of previously scheduled food availability is indicated by dotted lines in the activity profiles. The light-dark cycle is indicated by the white and black bars, respectively.

Mentions: After restricted feeding and ad libitum access to food, rats exhibit activity at the approximate time of previous food availability during food deprivation [2]. FAA disappears during ad libitum feeding between restricted feeding and food deprivation, suggesting that rats must be sufficiently “hungry” or that some resource must be depleted beyond a critical level in order to observe FAA. FAA during food deprivation is easily observed in rats since they readily survive several days of fasting. In contrast, the length of food deprivation in mice must be limited to about 48 to 60 hours to ensure their survival. Therefore, the timing of food deprivation relative to the previous time of food availability may be critical for observing FAA during fasting. If food is removed only a few hours before the time of previous food availability, then mice may not be “hungry” enough to express FAA on the first day of food deprivation. To test this hypothesis, wildtype mice were fed for 4 hrs/day, from zeitgeber time (ZT) 6 to ZT10, for 9 days, then fed ad libitum for 6 days, and then wheel-running activity was assessed during 48 hours of food deprivation that began at either ZT3 (Fig. 1A, B) or ZT12 (Fig. 1C, D). When food was removed at ZT3 (Fig. 1B), minimal FAA was observed on the first day of food deprivation (72±55), but FAA increased significantly on the second day of fasting (2178±1261; p = 0.03). In contrast, FAA was robust on both the first (2187±3191) and second (5701±7547) days of food deprivation when food was removed at ZT12 (p = 0.37). It is possible that mice that began fasting at ZT3 were not “hungry” enough at ZT6 to display FAA on the first day of food deprivation. In contrast, mice that began fasting at ZT12 had 18 hours to become “hungry” and therefore displayed clear FAA at ZT6 the following day. Furthermore, FAA was observed on the second day of food deprivation in both conditions, suggesting that a certain period of food deprivation must be experienced before FAA is fully expressed. Since FAA was apparent on both days of fasting when food was removed at ZT12, we began fasting mice 18 hours before the time of previously scheduled food availability for all subsequent food deprivation experiments.


Robust food anticipatory activity in BMAL1-deficient mice.

Pendergast JS, Nakamura W, Friday RC, Hatanaka F, Takumi T, Yamazaki S - PLoS ONE (2009)

The timing of food deprivation affects food anticipatory activity (FAA).Diagrams of restricted feeding protocols when mice are food deprived starting at ZT3 (A) or ZT12 (C). Wildtype C57BL/6J mice were fed ad libitum and then food availability was gradually reduced (RF) from 8 hrs/day to 6 hrs/day. Then mice were fed 4 hrs/day (from ZT6 to ZT10) for at least 9 days and then provided food ad libitum for 6 days. The time when food was available is indicated by gray shading in A and C. On the seventh day of ad libitum feeding, food was removed at either ZT3 (A, B) or ZT 12 (C, D). Food was replaced 48 hrs later. Group average activity profiles for mice that began fasting at ZT3 (B; n = 4) or ZT12 (D; n = 5) were generated by averaging the number of wheel revolutions per 10-minute bin (black line) and were plotted relative to the light-dark cycle where ZT0 is the time of lights on and ZT12 is lights off. The SEM, which represents the variability among mice, is shown in dark gray shading. The time of previously scheduled food availability is indicated by dotted lines in the activity profiles. The light-dark cycle is indicated by the white and black bars, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654093&req=5

pone-0004860-g001: The timing of food deprivation affects food anticipatory activity (FAA).Diagrams of restricted feeding protocols when mice are food deprived starting at ZT3 (A) or ZT12 (C). Wildtype C57BL/6J mice were fed ad libitum and then food availability was gradually reduced (RF) from 8 hrs/day to 6 hrs/day. Then mice were fed 4 hrs/day (from ZT6 to ZT10) for at least 9 days and then provided food ad libitum for 6 days. The time when food was available is indicated by gray shading in A and C. On the seventh day of ad libitum feeding, food was removed at either ZT3 (A, B) or ZT 12 (C, D). Food was replaced 48 hrs later. Group average activity profiles for mice that began fasting at ZT3 (B; n = 4) or ZT12 (D; n = 5) were generated by averaging the number of wheel revolutions per 10-minute bin (black line) and were plotted relative to the light-dark cycle where ZT0 is the time of lights on and ZT12 is lights off. The SEM, which represents the variability among mice, is shown in dark gray shading. The time of previously scheduled food availability is indicated by dotted lines in the activity profiles. The light-dark cycle is indicated by the white and black bars, respectively.
Mentions: After restricted feeding and ad libitum access to food, rats exhibit activity at the approximate time of previous food availability during food deprivation [2]. FAA disappears during ad libitum feeding between restricted feeding and food deprivation, suggesting that rats must be sufficiently “hungry” or that some resource must be depleted beyond a critical level in order to observe FAA. FAA during food deprivation is easily observed in rats since they readily survive several days of fasting. In contrast, the length of food deprivation in mice must be limited to about 48 to 60 hours to ensure their survival. Therefore, the timing of food deprivation relative to the previous time of food availability may be critical for observing FAA during fasting. If food is removed only a few hours before the time of previous food availability, then mice may not be “hungry” enough to express FAA on the first day of food deprivation. To test this hypothesis, wildtype mice were fed for 4 hrs/day, from zeitgeber time (ZT) 6 to ZT10, for 9 days, then fed ad libitum for 6 days, and then wheel-running activity was assessed during 48 hours of food deprivation that began at either ZT3 (Fig. 1A, B) or ZT12 (Fig. 1C, D). When food was removed at ZT3 (Fig. 1B), minimal FAA was observed on the first day of food deprivation (72±55), but FAA increased significantly on the second day of fasting (2178±1261; p = 0.03). In contrast, FAA was robust on both the first (2187±3191) and second (5701±7547) days of food deprivation when food was removed at ZT12 (p = 0.37). It is possible that mice that began fasting at ZT3 were not “hungry” enough at ZT6 to display FAA on the first day of food deprivation. In contrast, mice that began fasting at ZT12 had 18 hours to become “hungry” and therefore displayed clear FAA at ZT6 the following day. Furthermore, FAA was observed on the second day of food deprivation in both conditions, suggesting that a certain period of food deprivation must be experienced before FAA is fully expressed. Since FAA was apparent on both days of fasting when food was removed at ZT12, we began fasting mice 18 hours before the time of previously scheduled food availability for all subsequent food deprivation experiments.

Bottom Line: We found that BMAL1-deficient mice displayed FAA during restricted feeding in 12hr light:12hr dark (12L:12D) and 18L:6D lighting cycles, but distinct activity during food deprivation was observed only in 18L:6D.While BMAL1-deficient mice also exhibited robust FAA during restricted feeding in constant darkness, mice were hyperactive during food deprivation so it was not clear that FAA consistently occurred at the time of previously scheduled food availability.Furthermore, the expression of FAA may be possible without a circadian oscillator that depends on BMAL1.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.

ABSTRACT
Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Even though nocturnal rodents prefer to forage at night, daytime food anticipatory activity (FAA) is observed prior to short meals presented at a scheduled time of day. Under this restricted feeding regimen, rodents exhibit two distinct bouts of activity, a nocturnal activity rhythm that is entrained to the light-dark cycle and controlled by the master clock in the suprachiasmatic nuclei (SCN) and a daytime bout of activity that is phase-locked to mealtime. FAA also occurs during food deprivation, suggesting that a food-entrainable oscillator (FEO) keeps time in the absence of scheduled feeding. Previous studies have demonstrated that the FEO is anatomically distinct from the SCN and that FAA is observed in mice lacking some circadian genes essential for timekeeping in the SCN. In the current study, we optimized the conditions for examining FAA during restricted feeding and food deprivation in mice lacking functional BMAL1, which is critical for circadian rhythm generation in the SCN. We found that BMAL1-deficient mice displayed FAA during restricted feeding in 12hr light:12hr dark (12L:12D) and 18L:6D lighting cycles, but distinct activity during food deprivation was observed only in 18L:6D. While BMAL1-deficient mice also exhibited robust FAA during restricted feeding in constant darkness, mice were hyperactive during food deprivation so it was not clear that FAA consistently occurred at the time of previously scheduled food availability. Taken together, our findings suggest that optimization of experimental conditions such as photoperiod may be necessary to visualize FAA in genetically modified mice. Furthermore, the expression of FAA may be possible without a circadian oscillator that depends on BMAL1.

Show MeSH
Related in: MedlinePlus