GHSR signalling in perinatal phases is involved in liver metabolism at puberty

in Journal of Endocrinology
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Marcos Divino Ferreira-Junior Laboratory of Endocrine Physiology and Metabolism, Department of Physiological Sciences, Federal University of Goias, Goiânia, Brazil
Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal

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Keilah Valéria Naves Cavalcante Laboratory of Endocrine Physiology and Metabolism, Department of Physiological Sciences, Federal University of Goias, Goiânia, Brazil

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Carlos Henrique Xavier Systems Neurobiology Laboratory, Department of Physiological Sciences, Federal University of Goias, Goiânia, Brazil

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Emerielle Cristine Vanzela Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

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Antonio Carlos Boschero Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

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Paulo Matafome University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal
University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal
Clinical and Academic Centre of Coimbra (CACC), Coimbra, Portugal
Polytechnic University of Coimbra, Coimbra Health School, H&T Research Center, Coimbra, Portugal

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Rodrigo Mello Gomes Laboratory of Endocrine Physiology and Metabolism, Department of Physiological Sciences, Federal University of Goias, Goiânia, Brazil
Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

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Correspondence should be addressed to M Ferreira-Junior: marcosdfjunior@ufg.br
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Ghrelin has effects that range from the maturation of the central nervous system to the regulation of energy balance. The production of ghrelin increases significantly during the first weeks of life. Studies have addressed the metabolic effects of liver-expressed antimicrobial peptide 2 (LEAP2) in inhibiting the effects evoked by ghrelin, mainly in glucose homeostasis, insulin resistance, and lipid metabolism. Despite the known roles of ghrelin in the postnatal development, little is known about the long-term metabolic influences of modulation with the endogenous expressed growth hormone secretagogue receptor (GHSR) inverse agonist LEAP2. This study aimed to evaluate the contribution of GHSR signalling during perinatal phases, to neurodevelopment and energy metabolism in young animals, under inverse antagonism by LEAP2[1–14]. For this, two experimental models were used: (i) LEAP2[1–14] injections in female rats during the pregnancy. (ii) Postnatal modulation of GHSR with LEAP2[1–14] or MK677. Perinatal GHSR modulation by LEAP2[1–14] impacts glucose homeostasis in a sex and phase-dependent manner, despite no effects on body weight gain or food intake. Interestingly, liver PEPCK expression was remarkably impacted by LEAP2 injections. The observed results suggests that perinatal LEAP2 exposure can modulate liver metabolism and systemic glucose homeostasis. In addition, these results, although not expressive, may just be the beginning of the metabolic imbalance that will occur in adulthood.

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