| Abstract No.: | A-E1172 |
| Country: | Canada |
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| Title: | GHRELIN FACILITATES ENTRAINMENT TO FEEDING SCHEDULES |
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| Authors/Affiliations: | 1 Ian Blum; 2 Ian Blum*; 3 Mark Sleeman; 3 Mark Sleeman; 4 Tamas Horvath; 4 Tamas Horvath; 1 Alfonso Abizaid; 1 Alfonso Abizaid*;
1 Carleton University Institute for Neuroscience, Ottawa, ON, Canada; 2 Carleton University Neuroscience Institute, Ottawa, ON, Canada; 3 Regeneron Pharmaceuticals, Tarrytown, USA; 4 Yale University School of Medicine, New Haven, USA
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| Content: | Objectives: Ghrelin, a hormone produced by the stomach, targets various brain regions to increase food intake and adiposity. Furthermore, ghrelin levels increase in animals that are fasted, and decrease soon after the onset of a feeding bout. Interestingly, ghrelin levels also peak in anticipation of meals in restricted feeding schedule paradigms.
Given these data, we hypothesized that ghrelin may be important for the entrainment of circadian rhythms to restricted feeding schedules.
Materials and Methods: Mice with targeted mutations to the ghrelin receptor gene (GHS-RKO) and their wild-type counterparts were used in this study. At the onset of the study, all animals were single housed in activity wheel housing units. The individual activities were measured as the number of wheel revolutions in 10-minute bins. Three days of baseline were recorded before the restricted feeding paradigm commenced. The main zeitgeiber, lights on, occurred at ZT0 with food being presented from ZT4-ZT8. This restricted feeding was carried out for 21 days and the total chow eaten by each mouse was monitored daily. After 20 hours of fasting the animals were then placed back on an ad libitum diet for 4 days. Research was conducted under the guidelines of the Canadian Council on Animal Care and approved by Carleton University’s Animal Care Committee.
Results: Wild types and GHSRKO mice were compared on several measures including food anticipatory activity (FAA) and duration, nocturnal activity and duration, and nocturnality (defined as nocturnal activity as a percentage of total daily activity), and overall activity using two-way ANOVAs followed by post-hoc tests.
Results show that while both groups exhibited FAA, the wildtype mice, on average, showed significant FAA after three days, while the GHSRKO mice required at least six days before showing FAA. Furthermore, even after entrainment has occurred, FAA in GHSRKO mice is lower than that of wild type mice even though nocturnal activity in mice from both groups does not differ. Finally, once the feeding schedule was removed, there were no differences in the amount of time that it took mice to return to a regular 12 hr. light/dark cycle.
Conclusions: GHS-RKO mice show a delay and attenuation of FAA as compared to wild type controls, suggesting that ghrelin facilitates the entrainment of locomotor activity rhythms to restricted feeding schedules. Ghrelin, however, does not appear to be important in the entrainment to photic cues.
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