Blocking Leptin Action One Week After Weaning Reverts most of the Programming Caused by Neonatal Hyperleptinemia in the Adult Rat

P. A. Trotta; E. G. Moura; J. G. Franco; N. S. Lima; E. de Oliveira; A. Cordeiro; L. L. Souza; K. J. Oliveira; P. C. Lisboa; C. C. Pazos Moura; M. C. F. Passos

doi:10.1055/s-0031-1271694

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2011; 43(3): 171-177
DOI: 10.1055/s-0031-1271694

Original Basic

Blocking Leptin Action One Week After Weaning Reverts most of the Programming Caused by Neonatal Hyperleptinemia in the Adult Rat

P. A. Trotta¹ , E. G. Moura¹ , J. G. Franco¹ , N. S. Lima¹ , E. de Oliveira¹ , A. Cordeiro² , L. L. Souza² , K. J. Oliveira³ , P. C. Lisboa¹ , C. C. Pazos Moura² , M. C. F. Passos¹

¹Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, RJ, Brazil
²Biophysic Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, RJ, Brazil
³Fluminense Federal University, Niterói, RJ, Brazil

Abstract

Hyperleptinemia during lactation programs for higher serum leptin in 30-day-old and adult rats, associated with metabolic changes. Here we evaluated the inhibition of serum leptin at 29 and 30 days on the metabolic phenotype of rats programmed with leptin during lactation. Pups from Wistar rats were saline-injected or leptin-injected from postnatal day 1 to day 10. At 29 and 30 days old, animals were injected with anti-leptin antibody (LA and CA) or saline (LS and CS). In adult animals, higher visceral (+53%) and total fat mass (+33%), hyperleptinemia (+67%), hypertriglyceridemia (+47%), and hypoadiponectinemia (−44%) observed in LS group compared to CS were prevented by immunoneutralization of leptin, since LA group had those parameters values similar to CS group. However, immunoblockade of leptin in normal animals led to the same metabolic changes seen in leptin-treated animals, in addition to lower serum adiponectin (−77% vs. CS) and higher insulin resistance index (+37%). Liver sirtuin1 (SIRT1) was higher (+41%) only in LA group, suggesting a role for SIRT1 in the prevention of leptin programming. Hypothalamic OBR was lower and SOCS3 higher in LS group and these changes were normalized in LA group. In conclusion, blocking leptin action one week after weaning seems to revert most of the alterations observed in rats programmed by neonatal hyperleptinemia. Higher liver SIRT1 expression may be one of the mechanisms involved, leading to a better glucose and lipid metabolism. Our data suggest that the lack or the excess of leptin programs an adverse metabolic phenotype in adulthood.

Key words

leptin antibody - lactation - programming - hyperleptinemia

Full Text

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Correspondence

Prof. E. Gaspar de MouraPhD

Departamento de Ciências

Fisiológicas – 5° andar

Instituto de Biologia

Universidade do Estado do Rio

de Janeiro

Av. 28 de setembro

87-Rio de Janeiro

20551-030 RJ

Brazil

Phone: +55/21/258 76 434

Fax: +55/21/258 76 129

Email: egbertomoura@globo.com