Silvia Barja-Fernández1,2,3, Javier Lugilde4, Cecilia Castelao1,2, Rocío Vázquez-Cobela2,3, Luisa M Seoane1,2, Carlos Diéguez2,4, Rosaura Leis5,6, Sulay Tovar7,8. 1. Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo. Hospitalario Universitario de Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain. 2. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Santiago de Compostela, 15706, Spain. 3. Departamento Pediatría, GI Nutrición Pediátrica (IDIS,CHUS), Unidad de investigación de Galicia de desarrollo, crecimiento y nutrición humana. Universidade de Santiago de Compostela (USC), 15706, Santiago de Compostela, Spain. 4. Departamento de Fisioloxía and Centro de Investigación en Medicina Molecular y Enfermedades Cronicas (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, 15782, Spain. 5. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Santiago de Compostela, 15706, Spain. mariarosaura.leis@usc.es. 6. Departamento Pediatría, GI Nutrición Pediátrica (IDIS,CHUS), Unidad de investigación de Galicia de desarrollo, crecimiento y nutrición humana. Universidade de Santiago de Compostela (USC), 15706, Santiago de Compostela, Spain. mariarosaura.leis@usc.es. 7. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Santiago de Compostela, 15706, Spain. sulay.tovar@usc.es. 8. Departamento de Fisioloxía and Centro de Investigación en Medicina Molecular y Enfermedades Cronicas (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, 15782, Spain. sulay.tovar@usc.es.
Abstract
BACKGROUND/ OBJECTIVES: Liver-expressed antimicrobial peptide 2 (LEAP-2) was recently identified as an endogenous non-competitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a). LEAP-2 blunts ghrelin-induced feeding and its plasma levels are modulated in response to nutritional status in humans. Despite the relevant role of ghrelin in childhood, puberty, and childhood obesity, the potential implication of LEAP-2 in these aspects remains totally unknown. We aimed to investigate the regulation of circulating plasma LEAP-2 in childhood and adolescent either lean or obese. METHODS AND RESULTS: Plasma levels of LEAP-2 were analyzed in a cross-sectional study with lean and obese children and adolescents (n = 150). Circulating LEAP-2 levels were significantly higher in girls than in boys independently of whether they were obese or lean. In addition, LEAP-2 was significantly increased (p < 0.001) in pubertal than in prepubertal girls, while no changes were found in boys between both developmental stages. Moreover, in girls LEAP-2 was positively correlated with insulin, IGF-1, HOMA-IR and triglycerides and negatively with ghrelin. In boys, LEAP-2 was positively correlated with leptin and negatively with vitamin D levels. CONCLUSION: This study reveals a sexual dimorphism in LEAP-2 levels in children and adolescents. These changes and the higher levels during puberty imply that LEAP-2 may contribute to some of the biological adaptations occurring during pubertal development in terms of food intake, energy balance, growth rate, and puberty onset. Future studies assessing LEAP-2 levels in longitudinal studies and its implications in growth rate, puberty onset, and reproductive hormones will help to understand the relevance of this hormone in this stage of life.
BACKGROUND/ OBJECTIVES: Liver-expressed antimicrobial peptide 2 (LEAP-2) was recently identified as an endogenous non-competitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a). LEAP-2 blunts ghrelin-induced feeding and its plasma levels are modulated in response to nutritional status in humans. Despite the relevant role of ghrelin in childhood, puberty, and childhood obesity, the potential implication of LEAP-2 in these aspects remains totally unknown. We aimed to investigate the regulation of circulating plasma LEAP-2 in childhood and adolescent either lean or obese. METHODS AND RESULTS: Plasma levels of LEAP-2 were analyzed in a cross-sectional study with lean and obese children and adolescents (n = 150). Circulating LEAP-2 levels were significantly higher in girls than in boys independently of whether they were obese or lean. In addition, LEAP-2 was significantly increased (p < 0.001) in pubertal than in prepubertal girls, while no changes were found in boys between both developmental stages. Moreover, in girls LEAP-2 was positively correlated with insulin, IGF-1, HOMA-IR and triglycerides and negatively with ghrelin. In boys, LEAP-2 was positively correlated with leptin and negatively with vitamin D levels. CONCLUSION: This study reveals a sexual dimorphism in LEAP-2 levels in children and adolescents. These changes and the higher levels during puberty imply that LEAP-2 may contribute to some of the biological adaptations occurring during pubertal development in terms of food intake, energy balance, growth rate, and puberty onset. Future studies assessing LEAP-2 levels in longitudinal studies and its implications in growth rate, puberty onset, and reproductive hormones will help to understand the relevance of this hormone in this stage of life.
Authors: Stephanie Holm; Anna S Husted; Louise J Skov; Thomas H Morville; Christoffer A Hagemann; Tina Jorsal; Morten Dall; Alexander Jakobsen; Anders B Klein; Jonas T Treebak; Filip K Knop; Thue W Schwartz; Christoffer Clemmensen; Birgitte Holst Journal: Endocrinology Date: 2022-06-01 Impact factor: 5.051
Authors: Javier Lugilde; Sabela Casado; Daniel Beiroa; Juan Cuñarro; Montserrat Garcia-Lavandeira; Clara V Álvarez; Rubén Nogueiras; Carlos Diéguez; Sulay Tovar Journal: Cells Date: 2022-01-19 Impact factor: 6.600