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

Autor(es)

Ramos-Lobo, Angela M. ^[1] ; Teixeira, Pryscila D. S. ^[1] ; Furigo, Isadora C. ^[1] ; Melo, Helen M. ^[2] ; Lyra e Silva, Natalia de M. ^{[2, 3]} ; De Felice, Fernanda G. ^[2] ; Donato, Jr., Jose ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro - Brazil

^[3] Queens Univ, Dept Psychiat, Ctr Neurosci Studies, Kingston, ON - Canada

• Tipo de documento: Artigo Científico
• Fonte: eLIFE; v. 8, JAN 29 2019.
• Citações Web of Science: 3

Resumo

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. (AU)

• Processo FAPESP: 15/10992-6 - Estudo da programação metabólica por meio de diferentes abordagens
• Beneficiário: Jose Donato Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/11752-6 - Estudo das funções da leptina durante o período intrauterino e infância no camundongo
• Beneficiário: Angela Maria Ramos Lobo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/09679-4 - Estudo dos efeitos centrais do hormônio do crescimento sobre o metabolismo energético e controle glicêmico
• Beneficiário: Isadora Clivatti Furigo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado