ESPE Abstracts (2015) 84 P-3-859

Long-Term Effects of Neonatal Over-Nutrition on Metabolic Equilibrium are Age and Sex Dependant

Pilar Argente-Arizóna,b, Purificación Rosb,c, Francisca Díaza, Esther Fuente-Martína,b, Vicente Barriosa, Julie A Chowena & Jesús Argentea,b


aDepartment of Endocrinology, Instituto de Investigación la Princesa, Hospital Infantil Universitario Niño Jesús, CIBEROBN, Madrid, Spain; bDepartment of Paediatrics, Universidad Autónoma de Madrid, Madrid, Spain; cDepartment of Paediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain


Background: Neonatal over-nutrition (NON) can have a long-term effects on energy homeostasis and some of these effects may be sexually dimorphic.

Objective and hypotheses: We aimed to determine how NON affects body weight (BW), body composition and cytokine levels throughout development and if these changes are sexually dimorphic. We hypothesised that the effects would be both age and sex dependant.

Methods: At birth, Wistar rats were organized into litters of four (NON) or 12 (control) pups (equal number males/females) and killed on postnatal days (P) 10, 21 (weaning), 30, 50, 85 or 150. Serum levels of adiponectin, leptin, insulin, interleukins (IL) six and 1β and TNFα and cytokine mRNA levels in s.c. and visceral (V) adipose tissue were measured.

Results: At P10 BW was greater in NON rats of both sexes (P<0.0001), continuing until P60. After P90 NON again increased BW in males (P<0.0001). At P10 SC was increased by NON, with females more affected than males (P<0.0001). These effects were not found after P21, but at P150 NON again increased SC in males. At P21 NON increased V (P<0.001) and males had more V than females (P<0.0001). The effect of NON disappeared after P50 and returned in later adulthood, but only in males. At P10 serum glucose (P<0.02), insulin (P<0.0001), leptin (P<0.03) and adiponectin (P<0.0001) were increased and IL1β (P<0.05) and TNFα (P<0.0006) levels decreased by NON, with similar changes in cytokine expression in s.c. None of these effects were found at P30. Thus, there is an early effect of NON that dissipates and then reappears in males after P90, increasing BW, V, s.c., serum leptin levels and TNF-α gene expression in V.

Conclusion: Early nutritional modifications can have long-term effects that are both age and sex dependant and that may possibly affect the aging of metabolic homeostasis.

Funding: This work was funded by grants from Fondos de Investigación Sanitaria (grant numbers PI100747, PI1302195), Ministerio de Ciencia e Innovación (grant number BFU2011–27492), Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, and Fundación de Endocrinología y Nutrición.

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