title: Age and sex dependent effects of early overnutrition on metabolic parameters and the role of neonatal androgens.
abstract: BACKGROUND
  Males and females respond differently to diverse metabolic situations. Being raised in a small litter is reported to cause overnutrition that increases weight gain and predisposes an individual to metabolic disturbances in adulthood; however, existing data are inconsistent. Indeed, significant weight gain and/or metabolic disturbances, such as hyperinsulinemia and hyperleptinemia, are sometimes not encountered. We hypothesized that these inconsistencies could be due to the animal's sex and/or age at which metabolic parameters are measured.
  
  
  METHODS
  To analyze the effects of neonatal overnutrition, male and female Wistar rats were raised in litters of 4 or 12 pups/dam and killed at postnatal days (PND) 10, 21, 30, 50, 85, or 150. In a second study to determine if neonatal sex steroid levels influence sex differences in metabolic parameters, female rats were treated with testosterone on PND1. Effects on weight, length, fat pads, adipokine production, and serum levels of glucose, metabolic hormones, and cytokines were analyzed in both studies.
  
  
  RESULTS
  By PND10, both males and females raised in small litters had increased body weight, body length, adiposity, and serum glucose, insulin, leptin, and adiponectin levels. Females had a greater increase in inguinal fat, and males had higher expression of leptin messenger RNA (mRNA) and serum insulin, as well as increased testosterone levels. Most of the litter size effects diminished or disappeared after weaning and reappeared during adulthood in males, with sex differences in body size and adiposity being apparent postpubertally. Treatment of females with testosterone on PND1 tended to masculinize some metabolic parameters in adulthood such as increased body weight and serum leptin levels.
  
  
  CONCLUSIONS
  Our results indicate that (1) both sex and age determine the response to neonatal overnutrition; (2) differences in neonatal sex steroid levels may participate in the development of sex differences in metabolic parameters in adulthood and possibly in the response to neonatal overnutrition; and (3) the comparison of circulating hormone and cytokine levels, even in normal control animals, should take into consideration the early neonatal nutritional environment.
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avenida Menéndez Pelayo 65, Madrid, 28009 Spain ; Department of Pediatrics, Universidad Autónoma of Madrid, Madrid, Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Argente-Arizón
authors.affiliation: Department of Pediatrics, Universidad Autónoma of Madrid, Madrid, Spain ; Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: Ros
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avenida Menéndez Pelayo 65, Madrid, 28009 Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Díaz
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avenida Menéndez Pelayo 65, Madrid, 28009 Spain ; Department of Pediatrics, Universidad Autónoma of Madrid, Madrid, Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Fuente-Martin
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avenida Menéndez Pelayo 65, Madrid, 28009 Spain ; Department of Pediatrics, Universidad Autónoma of Madrid, Madrid, Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Castro-González
authors.affiliation: Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain ; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC/HURS), Córdoba, 14004 Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Sánchez-Garrido
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avenida Menéndez Pelayo 65, Madrid, 28009 Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Barrios
authors.affiliation: Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain ; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC/HURS), Córdoba, 14004 Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Tena-Sempere
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avenida Menéndez Pelayo 65, Madrid, 28009 Spain ; Department of Pediatrics, Universidad Autónoma of Madrid, Madrid, Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avenida Menéndez Pelayo 65, Madrid, 28009 Spain ; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
keywords: Litter size; Metabolic hormones; Neonatal nutrition; Neonatal testosterone; Sex differences