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Am J Physiol Regul Integr Comp Physiol 289: R353-R358, 2005. First published April 7, 2005; doi:10.1152/ajpregu.00756.2004
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Physiological Regulation of Appetite

Ghrelin is an orexigenic and metabolic signaling peptide in the arcuate and paraventricular nuclei

Paul J. Currie,1 Aaisha Mirza,1 Rebecca Fuld,1 Diana Park,1 and Joseph R. Vasselli2

1Department of Psychology, Barnard College, Columbia University, New York, New York; and 2New York Obesity Research Center, St. Luke's-Roosevelt Hospital Center, New York, New York

Submitted 5 November 2004 ; accepted in final form 5 April 2005

Ghrelin is a 28-amino acid acylated peptide and is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The GHS-R is expressed in hypothalamic nuclei, including the arcuate nucleus (Arc) where it is colocalized with neuropeptide Y (NPY) neurons. In the present study, we examined the effects of ghrelin on feeding and energy substrate utilization (respiratory quotient; RQ) following direct injections into either the arcuate or the paraventricular nucleus (PVN) of the hypothalamus. Ghrelin was administered at the beginning of the dark cycle at doses of 15–60 pmol to male and female rats. In feeding studies, food intake was measured 2 and 4 h postinjection. Separate groups of rats were injected with ghrelin, and the RQ (CO2/O2) was measured using an open circuit calorimeter over a 4-h period. Both Arc and PVN injections of ghrelin increased food intake in male and female rats. Ghrelin also increased RQ, reflecting a shift in energy substrate utilization in favor of carbohydrate oxidation. Because these effects are similar to those observed after PVN injection of NPY, we then assessed the impact of coinjecting ghrelin with NPY into the PVN. When rats were pretreated with very low doses of ghrelin (2.5–10 pmol), NPY's (50 pmol) effects on eating and RQ were potentiated. Overall, these data are in agreement with evidence suggesting that ghrelin functions as a gut-brain endocrine hormone implicated in the regulation of food intake and energy metabolism. Our findings are also consistent with a possible interactive role of hypothalamic ghrelin and NPY systems.

energy substrate utilization; food intake; hypothalamus; respiratory quotient


Address for reprint requests and other correspondence: P. J. Currie, Dept. of Psychology, Barnard College, Columbia Univ., New York, New York 10027 (E-mail: pjc37{at}columbia.edu)




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