1. Neuroscience
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Long-term consequences of the absence of leptin signaling in early life

  1. Angela M Ramos-Lobo
  2. Pryscila DS Teixeira
  3. Isadora C Furigo
  4. Helen M Melo
  5. Natalia M Lyra e Silva
  6. Fernanda G De Felice
  7. Jose Donato  Is a corresponding author
  1. University of São Paulo, Brazil
  2. Federal University of Rio de Janeiro, Brazil
Research Article
  • Cited 19
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Cite this article as: eLife 2019;8:e40970 doi: 10.7554/eLife.40970

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.

Article and author information

Author details

  1. Angela M Ramos-Lobo

    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  2. Pryscila DS Teixeira

    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  3. Isadora C Furigo

    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  4. Helen M Melo

    Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  5. Natalia M Lyra e Silva

    Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  6. Fernanda G De Felice

    Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  7. Jose Donato

    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
    For correspondence
    jdonato@icb.usp.br
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4166-7608

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).

Reviewing Editor

  1. Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States

Publication history

  1. Received: August 31, 2018
  2. Accepted: January 28, 2019
  3. Accepted Manuscript published: January 29, 2019 (version 1)
  4. Version of Record published: February 21, 2019 (version 2)

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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Further reading

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