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SOCS3 ABLATION IN SF1 CELLS CAUSES MODEST METABOLIC EFFECTS DURING PREGNANCY AND LACTATION

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Autor(es):
Ramos-Lobo, Angela M. [1] ; Teixeira, Pryscila D. S. [1] ; Furigo, Isadora C. [1] ; Donato, Jr., Jose [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508000 Sao Paulo, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Neuroscience; v. 365, p. 114-124, DEC 4 2017.
Citações Web of Science: 5
Resumo

Previous studies have shown that leptin resistance is a key feature that leads to gestational metabolic adaptions. We hypothesized that leptin sensitivity In the ventromedial nucleus of the hypothalamus (VMH) plays a critical role regulating gestational metabolic changes. In the present study, we generated a mouse model carrying ablation of the suppressor of cytokine signaling 3 (SOCS3) in steroidogenic factor-1 (SF1) cells, which include the VMH, in order to investigate whether Increased leptin sensitivity In this neuronal population prevents at least part of the metabolic changes typically observed during gestation and lactation. As predicted by the inhibitory effects of SOCS3 In leptin signaling, pregnant SF1 SOCS3 KO mice exhibited Increased leptin sensitivity In the VMH, since an acute leptin injection induced a 95% Increase In the STAT3 phosphorylation in this nucleus, compared to control animals (p = 0.02). Despite that, SF1 SOCS3 KO mice showed similar weight gain, food intake, hypothalamic neuropeptide expression and serum leptin levels during pregnancy compared to control littermates. Unexpectedly, SF1 SOCS3 KO mice exhibited glucose intolerance during pregnancy. SF1 SOCS3 KO mice also presented a lower body weight (-3%; p < 0.05) during mid and late lactation, although food intake, litter size and offspring growth were not affected. Our findings suggest that Increased leptin sensitivity In the VMH causes modest metabolic effects and Is not sufficient to prevent major metabolic adaptations of pregnancy and lactation. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

Processo FAPESP: 13/21722-4 - Estudo do mecanismo de ação da Bromocriptina e de antagonistas de prolactina no tratamento do Diabetes Mellitus tipo 2 e da Obesidade.
Beneficiário:Isadora Clivatti Furigo
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 10/18086-0 - Bases moleculares da resistência à leptina
Beneficiário:Jose Donato Junior
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 14/11752-6 - Estudo das funções da leptina durante o período intrauterino e infância no camundongo
Beneficiário:Angela Maria Ramos Lobo
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 15/10992-6 - Estudo da programação metabólica por meio de diferentes abordagens
Beneficiário:Jose Donato Junior
Linha de fomento: Auxílio à Pesquisa - Regular