The effects of Ghrelin on body fluid homeostasis
Mietlicki, Elizabeth Genevieve
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Ghrelin is a gut peptide that increases food intake and traditionally has been studied for its role in energy homeostasis. In addition to its hyperphagic effects, an emerging body of literature describes a role for ghrelin in body fluid homeostasis. Ghrelin attenuates water intake in both mammalian and non-mammalian species. In rats, central administration of ghrelin reduces drinking under some, but not all, conditions that increase water intake. Body fluid homeostasis, however, requires the regulation of not only water intake but also salt intake. Previous studies examining the effects of ghrelin on fluid balance have focused on its effects on water intake. The experiments included in this dissertation tested the hypothesis that ghrelin reduces saline intake under a variety of natriorexigenic (salt intake-stimulating) conditions. The results provide evidence for a role of ghrelin in the regulation of NaCl intake. Specifically, intracerebroventricular administration of ghrelin reduced hypertonic saline intake in response to two natriorexigenic stimuli: central angiotensin II, and fluid deprivation followed by partial rehydration. In contrast, central ghrelin administration had no effect on hypertonic saline intake stimulated by peripheral polyethylene glycol (PEG). Additional studies examining the effects of ghrelin on water intake stimulated by PEG suggest that the effect of ghrelin on PEG-induced water intake may be more method-bound than previously reported. Despite a published report describing an anti-dipsogenic effect of ghrelin on PEG-induced water intake in a one-bottle test, two separate experiments in this dissertation found no effect of ghrelin on water intake under similar conditions. The anti-natriorexigenic effect of ghrelin described here is a new role for ghrelin in ingestive behavior and provides a potentially important foundation for future studies on the mechanisms by which ghrelin affects fluid intake.