title: Blockage of the Neonatal Leptin Surge Affects the Gene Expression of Growth Factors, Glial Proteins, and Neuropeptides Involved in the Control of Metabolism and Reproduction in Peripubertal Male and Female Rats.
abstract: Leptin (Lep) is important in the development of neuroendocrine circuits involved in metabolic control. Because both Lep and metabolism influence pubertal development, we hypothesized that early changes in Lep signaling could also modulate hypothalamic (HT) systems involved in reproduction. We previously demonstrated that a single injection of a Lep antagonist (Antag) on postnatal day (PND)9, coincident with the neonatal Lep peak, induced sexually dimorphic modifications in trophic factors and markers of cell turnover and neuronal maturation in the HT on PND13. Here, our aim was to investigate whether the alterations induced by Lep antagonism persist into puberty. Accordingly, male and female rats were treated with a pegylated super Lep Antag from PND5 to PND9 and killed just before the normal appearance of external signs of puberty (PND33 in females and PND43 in males). There was no effect on body weight, but in males food intake increased, subcutaneous adipose tissue decreased and HT neuropeptide Y and Agouti-related peptide mRNA levels were reduced, with no effect in females. In both sexes, the Antag increased HT mRNA levels of the kisspeptin receptor, G protein-coupled recepter 54 (Gpr54). Expression of the Lep receptor, trophic factors, and glial markers were differently affected in the HT of peripubertal males and females. Lep production in adipose tissue was decreased in Antag-treated rats of both sexes, with production of other cytokines being differentially regulated between sexes. In conclusion, in addition to the long-term effects on metabolism, changes in neonatal Lep levels modifies factors involved in reproduction that could possibly affect sexual maturation.
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: Virginia
authors: V
authors: Mela
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: Francisca
authors: F
authors: Díaz
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: Ana Belen
authors: AB
authors: Lopez-Rodriguez
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: María Jesús
authors: MJ
authors: Vázquez
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: Arieh
authors: A
authors: Gertler
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: Jesús
authors: J
authors: Argente
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: Manuel
authors: M
authors: Tena-Sempere
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: María-Paz
authors: MP
authors: Viveros
authors: Department of Physiology (Animal Physiology II) (V.M., A.B.L.-R., M.-P.V.), Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain; Department of Endocrinology (F.D., J.A., J.A.C.), Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa, 28009 Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de Obesidad y Nutrición (F.D., M.J.V., J.A., M.T.-S., J.A.C.), Instituto Carlos III, 28903 Madrid, Spain; Department of Cell Biology, Physiology, and Immunology (M.J.V., M.T.-S.), University of Córdoba and Instituto Maimónides de Investigación Biomédica, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain; and The Robert H. Smith Faculty of Agriculture, Food and Environment (A.G.), The Hebrew University of Jerusalem, Rehovot, Israel 76100.
authors: Julie A
authors: JA
authors: Chowen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D054369:Agouti-Related Protein / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004435:Eating / Q000235:genetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics; D020869:Gene Expression Profiling; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000235:genetics; D007986:Luteinizing Hormone / Q000235:genetics; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D054411:Receptors, Leptin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D012741:Sexual Maturation / Q000235:genetics*; D050151:Subcutaneous Fat; D014746:Vimentin / Q000235:genetics
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D009479:Neuropeptides; D012333:RNA, Messenger; D054411:Receptors, Leptin; D014746:Vimentin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone