Long-term consequences of the absence of leptin signaling in early life
- University of São Paulo, Brazil
- Federal University of Rio de Janeiro, Brazil
Abstract
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 4th or 10th 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.
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Individual values were plotted in each figure and source data files have also been included.
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Author details
Funding
Fundação de Amparo à Pesquisa do Estado de São Paulo (15/10992-6)
- Jose Donato
Fundação de Amparo à Pesquisa do Estado de São Paulo (14/11752-6)
- Angela M Ramos-Lobo
Fundação de Amparo à Pesquisa do Estado de São Paulo (16/09679-4)
- Isadora C Furigo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were carried out in compliance with NIH guidelines for the care and use of laboratory animals and were previously approved by our Institutional Animal Ethics Committee (protocol number 137/2013).
Copyright
© 2019, Ramos-Lobo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Long-term consequences of the absence of leptin signaling in early life
eLife 8:e40970.
https://doi.org/10.7554/eLife.40970
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