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Single gene deletions of orexin, leptin, neuropeptide Y, and ghrelin do not appreciably alter food anticipatory activity in mice.

Gunapala KM, Gallardo CM, Hsu CT, Steele AD - PLoS ONE (2011)

Bottom Line: Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents.NPY deletion did not alter the behavior or physiological response to CR.Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA.

View Article: PubMed Central - PubMed

Affiliation: Broad Fellows Program in Brain Circuitry, Division of Biology, California Institute of Technology, Pasadena, California, United States of America.

ABSTRACT
Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA.

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Calorie restriction of orexin knockout mice.(A) Body weights of orexin KO and WT mice on AL and CR feeding conditions. (B) Percent gain and loss of weight relative day 0 of the experiment. Orexin KO mice are resistant to weight loss when compared with WT CR mice (C) Fraction of time engaged in high activity behaviors (sum of hanging, jumping, rearing and walking) observed on day -7. (D) Fraction of time engaged in food bin entry, (E) fraction of time engaged in hanging, (F) fraction of time engaged in jumping, (G) fraction of time spent rearing, (H) fraction of time spent walking, and (I) fraction of behavior of spent in a resting state on day -7 of the experiment. n = 12 orexin KO and n = 23 orexin WT. (J) High activity behaviors during the 3 hrs prior to scheduled meal delivery (ZT 7–9) for WT mice on AL (n = 18) and CR (n = 9) and (K) Orexin KO mice on AL and CR (n = 6 for both groups). Statistics were performed using Mann-Whitney Test *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent the IQR for behavioral data and SEM for body weight data.
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pone-0018377-g002: Calorie restriction of orexin knockout mice.(A) Body weights of orexin KO and WT mice on AL and CR feeding conditions. (B) Percent gain and loss of weight relative day 0 of the experiment. Orexin KO mice are resistant to weight loss when compared with WT CR mice (C) Fraction of time engaged in high activity behaviors (sum of hanging, jumping, rearing and walking) observed on day -7. (D) Fraction of time engaged in food bin entry, (E) fraction of time engaged in hanging, (F) fraction of time engaged in jumping, (G) fraction of time spent rearing, (H) fraction of time spent walking, and (I) fraction of behavior of spent in a resting state on day -7 of the experiment. n = 12 orexin KO and n = 23 orexin WT. (J) High activity behaviors during the 3 hrs prior to scheduled meal delivery (ZT 7–9) for WT mice on AL (n = 18) and CR (n = 9) and (K) Orexin KO mice on AL and CR (n = 6 for both groups). Statistics were performed using Mann-Whitney Test *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent the IQR for behavioral data and SEM for body weight data.

Mentions: Under AL feeding conditions, both C57BL/6 orexin KO mice and WT littermate controls gained weight (Fig. 2A). Under the CR feeding conditions (beginning on day 0), orexin KO mice lost weight but not as severely as the WT controls (Fig. 2A). Food intake for orexin WT mice was 4.91±0.8 and 4.81±1.0 for orexin KO mice (mean and SD). To examine the body weight changes more carefully, we normalized the data by dividing the weight at each measurement by the weight on day 0 prior to the start of CR and observed that orexin KO and WT mice had similar percent weight gains when on AL feeding conditions (Fig. 2B). However, on a CR diet, orexin KO mice appeared refractory to weight loss on CR, as orexin KO mice on CR maintained a significantly higher percentage of their starting body weight than WT controls on CR feeding conditions (P<0.05, Mann-Whitney) (Fig. 2B).


Single gene deletions of orexin, leptin, neuropeptide Y, and ghrelin do not appreciably alter food anticipatory activity in mice.

Gunapala KM, Gallardo CM, Hsu CT, Steele AD - PLoS ONE (2011)

Calorie restriction of orexin knockout mice.(A) Body weights of orexin KO and WT mice on AL and CR feeding conditions. (B) Percent gain and loss of weight relative day 0 of the experiment. Orexin KO mice are resistant to weight loss when compared with WT CR mice (C) Fraction of time engaged in high activity behaviors (sum of hanging, jumping, rearing and walking) observed on day -7. (D) Fraction of time engaged in food bin entry, (E) fraction of time engaged in hanging, (F) fraction of time engaged in jumping, (G) fraction of time spent rearing, (H) fraction of time spent walking, and (I) fraction of behavior of spent in a resting state on day -7 of the experiment. n = 12 orexin KO and n = 23 orexin WT. (J) High activity behaviors during the 3 hrs prior to scheduled meal delivery (ZT 7–9) for WT mice on AL (n = 18) and CR (n = 9) and (K) Orexin KO mice on AL and CR (n = 6 for both groups). Statistics were performed using Mann-Whitney Test *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent the IQR for behavioral data and SEM for body weight data.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3065493&req=5

pone-0018377-g002: Calorie restriction of orexin knockout mice.(A) Body weights of orexin KO and WT mice on AL and CR feeding conditions. (B) Percent gain and loss of weight relative day 0 of the experiment. Orexin KO mice are resistant to weight loss when compared with WT CR mice (C) Fraction of time engaged in high activity behaviors (sum of hanging, jumping, rearing and walking) observed on day -7. (D) Fraction of time engaged in food bin entry, (E) fraction of time engaged in hanging, (F) fraction of time engaged in jumping, (G) fraction of time spent rearing, (H) fraction of time spent walking, and (I) fraction of behavior of spent in a resting state on day -7 of the experiment. n = 12 orexin KO and n = 23 orexin WT. (J) High activity behaviors during the 3 hrs prior to scheduled meal delivery (ZT 7–9) for WT mice on AL (n = 18) and CR (n = 9) and (K) Orexin KO mice on AL and CR (n = 6 for both groups). Statistics were performed using Mann-Whitney Test *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent the IQR for behavioral data and SEM for body weight data.
Mentions: Under AL feeding conditions, both C57BL/6 orexin KO mice and WT littermate controls gained weight (Fig. 2A). Under the CR feeding conditions (beginning on day 0), orexin KO mice lost weight but not as severely as the WT controls (Fig. 2A). Food intake for orexin WT mice was 4.91±0.8 and 4.81±1.0 for orexin KO mice (mean and SD). To examine the body weight changes more carefully, we normalized the data by dividing the weight at each measurement by the weight on day 0 prior to the start of CR and observed that orexin KO and WT mice had similar percent weight gains when on AL feeding conditions (Fig. 2B). However, on a CR diet, orexin KO mice appeared refractory to weight loss on CR, as orexin KO mice on CR maintained a significantly higher percentage of their starting body weight than WT controls on CR feeding conditions (P<0.05, Mann-Whitney) (Fig. 2B).

Bottom Line: Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents.NPY deletion did not alter the behavior or physiological response to CR.Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA.

View Article: PubMed Central - PubMed

Affiliation: Broad Fellows Program in Brain Circuitry, Division of Biology, California Institute of Technology, Pasadena, California, United States of America.

ABSTRACT
Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA.

Show MeSH
Related in: MedlinePlus