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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity

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Autor(es):
Pedroso, Joao A. B. [1] ; Buonfiglio, Daniella C. [1] ; Cardinali, Lais I. [1] ; Furigo, Isadora C. [1] ; Ramos-Lobo, Angela M. [1] ; Tirapegui, Julio [2] ; Elias, Carol F. [3, 4, 5] ; Donato, Jr., Jose [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food Sci & Expt Nutr, BR-05508 Sao Paulo, SP - Brazil
[3] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 - USA
[4] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 - USA
[5] Univ Texas SW Med Ctr Dallas, Div Hypothalam Res, Dept Internal Med, Dallas, TX 75390 - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: MOLECULAR METABOLISM; v. 3, n. 6, p. 608-618, SEP 2014.
Citações Web of Science: 41
Resumo

Therapies that improve leptin sensitivity have potential as an alternative treatment approach against obesity and related comorbidities. We investigated the effects of Socs3 gene ablation in different mouse models to understand the role of SOCS3 in the regulation of leptin sensitivity, diet-induced obesity (DIO) and glucose homeostasis. Neuronal deletion of SOCS3 partially prevented DIO and improved glucose homeostasis. Inactivation of SOCS3 only in LepR-expressing cells protected against leptin resistance induced by HFD, but did not prevent DIO. However, inactivation of SOCS3 in LepR-expressing cells protected mice from diet-induced insulin resistance by increasing hypothalamic expression of K-atp channel subunits and c-Fos expression in POMC neurons. In summary, the regulation of leptin signaling by SOCS3 orchestrates diet induced changes on glycemic control. These findings help to understand the molecular mechanisms linking obesity and type 2 diabetes, and highlight the potential of SOCS3 inhibitors as a promising therapeutic approach for the treatment of diabetes. (C) 2014 The Authors. Published by Elsevier GmbH. (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