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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 NPY knockout mice.(A) Body weights of NPY KO and WT mice on AL and CR feeding conditions. (B) Percent gain and loss of weight relative to day 0. (C) High activity behaviors of NPY KO and WT mice on day -7. (D) Food bin entry (E) hang, (F) jump, (G) rear and (H) walk on day -7. Statistics were performed using the Mann-Whitney Test with post-test. Error bars represent IQRs. n = 16 WT and n = 18 KO. (I) Normalized high activity behaviors in the 3 hrs preceding feeding for WT CR and WT AL. (J) Normalized high activity behaviors in the 3 hrs preceding feeding for NPY KO CR and WT AL. Statistics were performed using the Mann-Whitney Test, *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent IQR. n = 8 for all groups at all time points in panels I and J.
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pone-0018377-g005: Calorie restriction of NPY knockout mice.(A) Body weights of NPY KO and WT mice on AL and CR feeding conditions. (B) Percent gain and loss of weight relative to day 0. (C) High activity behaviors of NPY KO and WT mice on day -7. (D) Food bin entry (E) hang, (F) jump, (G) rear and (H) walk on day -7. Statistics were performed using the Mann-Whitney Test with post-test. Error bars represent IQRs. n = 16 WT and n = 18 KO. (I) Normalized high activity behaviors in the 3 hrs preceding feeding for WT CR and WT AL. (J) Normalized high activity behaviors in the 3 hrs preceding feeding for NPY KO CR and WT AL. Statistics were performed using the Mann-Whitney Test, *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent IQR. n = 8 for all groups at all time points in panels I and J.

Mentions: Under AL feeding conditions, both 129SvJ NPY KO mice and WT controls gained weight (Fig. 5A–B). Under the CR feeding conditions, both NPY KO and WT controls lose a similar percent of weight (Fig. 5A–B). There was no difference in baseline high activity behaviors between NPY KO and WT mice on AL feeding (day -7) (Fig. 5C); however, the amount of food bin entry displayed by WT mice was significantly higher than for NPY KOs (Fig. 5D). Despite this difference in food bin entry, the food intake values for WT and NPY KO on AL were nearly identical, with WT mice consuming 5.7±2.3 grams and NPY KO mice consuming 4.7±0.8 grams of chow per day on average. We examined the individual high activity behaviors and saw that there were no significant differences in hanging (Fig. 5E), jumping (Fig. 5F), rearing (Fig. 5G) and walking (Fig. 5H). WT mice on CR began showing a statistically significant increase in the fraction of high activity during ZT 7–9 relative to AL controls starting on day 7 and onwards (Fig. 5I). NPY KO mice on a CR diet noticeably increased activity beginning on day 7 and began showing a statistically significant increase on day 14 onward (Fig. 5J). The lack of significant increase in FAA in NPY KO mice until day 14 could be interpreted as a delayed onset of FAA in NPY KO mice since FAA is significantly increased in NPY WT mice on CR from day 7 though it is clear that there is a strong trend toward increased activity in the three hrs preceding feeding at day 7 in the NPY KO mice on CR.


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 NPY knockout mice.(A) Body weights of NPY KO and WT mice on AL and CR feeding conditions. (B) Percent gain and loss of weight relative to day 0. (C) High activity behaviors of NPY KO and WT mice on day -7. (D) Food bin entry (E) hang, (F) jump, (G) rear and (H) walk on day -7. Statistics were performed using the Mann-Whitney Test with post-test. Error bars represent IQRs. n = 16 WT and n = 18 KO. (I) Normalized high activity behaviors in the 3 hrs preceding feeding for WT CR and WT AL. (J) Normalized high activity behaviors in the 3 hrs preceding feeding for NPY KO CR and WT AL. Statistics were performed using the Mann-Whitney Test, *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent IQR. n = 8 for all groups at all time points in panels I and J.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3065493&req=5

pone-0018377-g005: Calorie restriction of NPY knockout mice.(A) Body weights of NPY KO and WT mice on AL and CR feeding conditions. (B) Percent gain and loss of weight relative to day 0. (C) High activity behaviors of NPY KO and WT mice on day -7. (D) Food bin entry (E) hang, (F) jump, (G) rear and (H) walk on day -7. Statistics were performed using the Mann-Whitney Test with post-test. Error bars represent IQRs. n = 16 WT and n = 18 KO. (I) Normalized high activity behaviors in the 3 hrs preceding feeding for WT CR and WT AL. (J) Normalized high activity behaviors in the 3 hrs preceding feeding for NPY KO CR and WT AL. Statistics were performed using the Mann-Whitney Test, *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent IQR. n = 8 for all groups at all time points in panels I and J.
Mentions: Under AL feeding conditions, both 129SvJ NPY KO mice and WT controls gained weight (Fig. 5A–B). Under the CR feeding conditions, both NPY KO and WT controls lose a similar percent of weight (Fig. 5A–B). There was no difference in baseline high activity behaviors between NPY KO and WT mice on AL feeding (day -7) (Fig. 5C); however, the amount of food bin entry displayed by WT mice was significantly higher than for NPY KOs (Fig. 5D). Despite this difference in food bin entry, the food intake values for WT and NPY KO on AL were nearly identical, with WT mice consuming 5.7±2.3 grams and NPY KO mice consuming 4.7±0.8 grams of chow per day on average. We examined the individual high activity behaviors and saw that there were no significant differences in hanging (Fig. 5E), jumping (Fig. 5F), rearing (Fig. 5G) and walking (Fig. 5H). WT mice on CR began showing a statistically significant increase in the fraction of high activity during ZT 7–9 relative to AL controls starting on day 7 and onwards (Fig. 5I). NPY KO mice on a CR diet noticeably increased activity beginning on day 7 and began showing a statistically significant increase on day 14 onward (Fig. 5J). The lack of significant increase in FAA in NPY KO mice until day 14 could be interpreted as a delayed onset of FAA in NPY KO mice since FAA is significantly increased in NPY WT mice on CR from day 7 though it is clear that there is a strong trend toward increased activity in the three hrs preceding feeding at day 7 in the NPY KO mice on CR.

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