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Ghrelin treatment induces rapid and delayed increments of food intake: a heuristic model to explain ghrelin’s orexigenic effects

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Abstract

Ghrelin is a stomach-derived peptide hormone with salient roles in the regulation of energy balance and metabolism. Notably, ghrelin is recognized as the most powerful known circulating orexigenic hormone. Here, we systematically investigated the effects of ghrelin on energy homeostasis and found that ghrelin primarily induces a biphasic effect on food intake that has indirect consequences on energy expenditure and nutrient partitioning. We also found that ghrelin-induced biphasic effect on food intake requires the integrity of Agouti-related peptide/neuropeptide Y-producing neurons of the hypothalamic arcuate nucleus, which seem to display a long-lasting activation after a single systemic injection of ghrelin. Finally, we found that different autonomic, hormonal and metabolic satiation signals transiently counteract ghrelin-induced food intake. Based on our observations, we propose a heuristic model to describe how the orexigenic effect of ghrelin and the anorectic food intake-induced rebound sculpt a timely constrain feeding response to ghrelin.

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All data generated or analyzed during this study are included in this published article and are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank Dr. Marcelo Vatta from the University of Buenos Aires for providing CCK-8S.

Funding

This work was supported by grants from the Fondo para la Investigación Científica y Tecnológica (FONCyT, PICT2016-1084 and PICT2017-3196) and from CONICET (PUE-2017) to MP. MPC and GF were supported by CONICET.

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  1. Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology, IMBICE, Argentine Research Council (CONICET), Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP), Calle 526 S/N entre 10 y 11, PO Box 403, 1900, La Plata, Buenos Aires, Argentina

    María Paula Cornejo, Guadalupe García Romero, Gimena Fernández, Mirta Reynaldo & Mario Perello

  2. Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251, CNRS, Université de Paris, 75013, Paris, France

    Raphaël G. P. Denis & Serge Luquet

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  1. María Paula Cornejo
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  4. Gimena Fernández
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MPC, RGPD, GGR, GF, and MR performed the experiments. MPC, MP, RGPD, and SL designed the experiments and wrote the manuscript.

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Correspondence to Mario Perello.

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Cornejo, M.P., Denis, R.G.P., García Romero, G. et al. Ghrelin treatment induces rapid and delayed increments of food intake: a heuristic model to explain ghrelin’s orexigenic effects. Cell. Mol. Life Sci. 78, 6689–6708 (2021). https://doi.org/10.1007/s00018-021-03937-0

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