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Ghrelin: Neuropeptide Regulator of Metabolism

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Ghrelin in Health and Disease

Part of the book series: Contemporary Endocrinology ((COE,volume 10))

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Abstract

Ghrelin regulates hypothalamic circuits to increase food intake by modulating the activity of two neuronal populations in the arcuate nucleus of hypothalamus. Those neurons (NPY/AgRP and POMC) are considered “first-order” sensory neurons in the control of food intake. Ghrelin simultaneously stimulates orexigenic NPY/AgRP neuronal activity and suppresses POMC neuronal activity via inhibitory γ-aminobutyric acid (GABA)-eric inputs from active NPY/AgRP neurons. Recent data suggests that metabolic status regulates the function of ghrelin on energy homeostasis and neuronal function and it appears that ghrelin is not able to activate this neuronal circuit in diet-induced obese mice. Contrary to expectations from 10 years ago, ghrelin seems to be more important for the regulation of blood glucose levels during starvation than it is for acute regulation of food intake. This chapter establishes the hypothesis that ghrelin primarily functions during negative energy balance to promote survival. Consistent with this idea, during calorie restriction, ghrelin increases blood glucose and suppresses glucose-stimulated insulin secretion from the pancreas. This important adaptive mechanism prevents insulin-driven clearance of glucose from the blood during negative energy balance and thus maintains an immediate energy supply.

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Acknowledgements

This work was supported by NHMRC grant (606662) to PJE; a Monash Fellowship, Monash University, an Australian Research Council Future Fellowship, and NHMRC grant (546131) to ZBA; and a Pfizer Australia Research Fellowship, a VESKI Fellowship, and NHMRC grant (606662) to MAC.

Conflicts of interest: The authors have no conflicts of interest.

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  1. Department of Physiology, Monash University, Building 13F, Wellington Road, Clayton, VIC, 3800, Australia

    Pablo J. Enriori Ph.D., Zane B. Andrews Ph.D. & Michael Alexander Cowley Ph.D.

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  1. Pablo J. Enriori Ph.D.
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  2. Zane B. Andrews Ph.D.
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Correspondence to Michael Alexander Cowley Ph.D. .

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  1. , Department of Metabolism and Aging, The Scripps Research Institute Florida, Scripps Way 3B3 130, Jupiter, 33458, Florida, USA

    Roy G. Smith

  2. , Department of Medicine, University of Virginia, Ray C Hunt Drive 450, Charlottesville, 22908, Virginia, USA

    Michael O. Thorner

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Enriori, P.J., Andrews, Z.B., Cowley, M.A. (2012). Ghrelin: Neuropeptide Regulator of Metabolism. In: Smith, R., Thorner, M. (eds) Ghrelin in Health and Disease. Contemporary Endocrinology, vol 10. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-903-7_6

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  • DOI: https://doi.org/10.1007/978-1-61779-903-7_6

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