Long-term consequences of the absence of leptin signaling in early life
Angela M Ramos-Lobo,
Pryscila DS Teixeira,
Isadora C Furigo,
Helen M Melo,
Natalia de M Lyra e Silva,
Fernanda G De Felice,
Jose Donato Jr
Affiliations
Angela M Ramos-Lobo
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Pryscila DS Teixeira
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Isadora C Furigo
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Helen M Melo
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Natalia de M Lyra e Silva
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Centre for Neuroscience Studies, Department of Psychiatry, Queen's University, Kingston, Canada
Fernanda G De Felice
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Leptin regulates energy balance and also exhibits neurotrophic effects during critical developmental periods. However, the actual role of leptin during development is not yet fully understood. To uncover the importance of leptin in early life, the present study restored leptin signaling either at the fourth or tenth week of age in mice formerly null for the leptin receptor (LepR) gene. We found that some defects previously considered irreversible due to neonatal deficiency of leptin signaling, including the poor development of arcuate nucleus neural projections, were recovered by LepR reactivation in adulthood. However, LepR deficiency in early life led to irreversible obesity via suppression of energy expenditure. LepR reactivation in adulthood also led to persistent reduction in hypothalamic Pomc, Cartpt and Prlh mRNA expression and to defects in the reproductive system and brain growth. Our findings revealed that early defects in leptin signaling cause permanent metabolic, neuroendocrine and developmental problems.
