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JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia

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Abstract

Oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. The purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. The three growth hormone secretagogues behaved as full agonists of the growth hormone secretagogues receptor both in terms of ability to stimulate calcium mobilization in Chinese hamster ovary cells and stimulation of growth hormone release in neonatal rats. Adult rats were (i) treated with vehicle throughout (controls), or (ii) treated with cisplatin (days 1–3) and a growth hormone secretagogues or vehicle, (days 1–12). Body weight and food consumption were measured daily. Although all growth hormone secretagogues caused initial transient acute increases in food intake, the total amount of food eaten by controls and growth hormone secretagogues treated groups over the 12 experimental days was not significantly different. All groups pre-treated with cisplatin lost up to 5–10 % body weight in the first 4 days; they subsequently gained weight at a rate comparable with controls. Interestingly, rats which received JMV2894 demonstrated a faster gain in body weight than any other growth hormone secretagogues treated group and at the end of the protocol reached a weight similar to that of controls. JMV2894 did not stimulate perirenal and epididymal fat accumulation but reduced MuRF mRNA levels in skeletal muscles. In conclusion, our findings demonstrate that JMV2894 antagonizes cisplatin induced weight loss in rats and may prove useful in antagonizing cachexia associated with cancer and chemotherapy in humans.

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Funding

This work was supported in part by a research grant of the University of Milano-Bicocca (Fondo di Ateneo per la Ricerca to AT and VL).

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Authors and Affiliations

  1. Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    Elena Bresciani, Laura Rizzi, Laura Molteni, Monica Ravelli, Vittorio Locatelli & Antonio Torsello

  2. Department of Pharmacy - Drug Sciences, University of Bari, Bari, Italy

    Antonella Liantonio

  3. Max Mousseron Institute of Biomolecules UMR5247, CNRS, University of Montpellier, ENSCM, Montpellier, France

    Khoubaib Ben Haj Salah, Jean-Alain Fehrentz & Jean Martinez

  4. Department of Biology, Lakehead University, Thunder Bay, ON, P7B 5E1, Canada

    Robert J. Omeljaniuk

  5. Department of Biomedical, Metabolic and Neural Sciences, Laboratory of Experimental Epileptology, University of Modena and Reggio Emilia, Modena, Italy

    Giuseppe Biagini

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  1. Elena Bresciani
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Correspondence to Antonio Torsello.

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The authors declare that they have no competing interests.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Protocols involving animal use were in accordance with European Directive 2010/63/EU and approved by the Italian Ministry of Health and by the Committee on Animal Experimentation of the University of Milano-Bicocca.

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Bresciani, E., Rizzi, L., Molteni, L. et al. JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia. Endocrine 58, 106–114 (2017). https://doi.org/10.1007/s12020-016-1184-2

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  • DOI: https://doi.org/10.1007/s12020-016-1184-2

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