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

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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.

Original languageEnglish
Number of pages25
Early online date29 Jan 2019
Publication statusE-pub ahead of print - 29 Jan 2019
Externally publishedYes

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