The Food Entrainable Oscillator: The Ghrelin and Growth Hormone Secretagogue Story

Food availability is a potent external cue that can uncouple endogenous rhythmicity from the master circadian oscillator. It is driven by a largely unknown entity that encompasses a network of peripheral and central systems, the food entrainable oscillator (FEO). The orexigenic gut hormone ghrelin is associated with feeding, energy metabolism and has been proposed as an entrainment signal for the FEO. This thesis set out to manipulate the FEO through scheduled feeding paradigms while studying the influence of ghrelin on FEO outputs. Energy utilization patterns in response to a scheduled meal, as examined through indirect calorimetry, exhibited entrainment to the meal timing. We further demonstrated that restricted feeding paradigm entrained the energy utilization patterns, independently of the GHSR and circulating ghrelin. The influence of scheduled meals on the FEO was not limited to a negative energy balance, freely fed CD-1 male mice exhibited food anticipatory activity (FAA) and entrained to a scheduled snack of cookie dough during their non-active phase. Intriguingly, the development and entrainment of FAA is dependent on both the type of scheduled snack and the strain of the animal model used. Circulating ghrelin levels were not necessary in the development or maintenance of the entrainment of the FAA. However, central signaling of ghrelin, through its growth hormone secretagogue receptor (GHSR) may have a role in the development of the FAA in paradigms of a scheduled treats. Taken together these data present evidence that ghrelin and the GHSR are not critical in mediating the systems of the FEO and its respective outputs, under various feeding paradigms.