Leptin Resistance Is Not the Primary Cause of Weight Gain Associated With Reduced Sex Hormone Levels in Female Mice

Autor(es)

da Silva, Regina P. ^[1] ; Zampieri, Thais T. ^[2] ; Pedroso, Joao A. B. ^[2] ; Nagaishi, Vanessa S. ^[2] ; Ramos-Lobo, Angela M. ^[2] ; Furigo, Isadora C. ^[2] ; Camara, Niels O. ^[3] ; Frazao, Renata ^[1] ; Donato, Jr., Jose ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Endocrinology; v. 155, n. 11, p. 4226-4236, NOV 2014.
• Citações Web of Science: 16

Resumo

Several studies have shown that estrogens mimic leptin's effects on energy balance regulation. However, the findings regarding the consequences of reduced sex hormone levels on leptin sensitivity are divergent. In the present study, we employed different experimental paradigms to elucidate the interaction between estrogens, leptin, and energy balance regulation. We confirmed previous reports showing that ovariectomy caused a reduction in locomotor activity and energy expenditure leading mice to obesity and glucose intolerance. However, the acute and chronic anorexigenic effects of leptin were preserved in ovariectomized (OVX) mice despite their increased serum leptin levels. We studied hypothalamic gene expression at different time points after ovariectomy and observed that changes in the expression of genes involved in leptin resistance (suppressors of cytokine signaling and protein-tyrosine phosphatases) did not precede the early onset of obesity in OVX mice. On the contrary, reduced sex hormone levels caused an up-regulation of the long form of the leptin receptor (LepR), resulting in increased activation of leptin signaling pathways in OVX leptin-treated animals. The up-regulation of the LepR was observed in long-term OVX mice (30 d or 24 wk after ovariectomy) but not 7 days after the surgery. In addition, we observed a progressive decrease in the coexpression of LepR and estrogen receptor-alpha in the hypothalamus after the ovariectomy, resulting in a low percentage of dual-labeled cells in OVX mice. Taken together, our findings suggest that the weight gain caused by reduced sex hormone levels is not primarily caused by induction of a leptin-resistance state. (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: 13/16374-7 - Interação entre leptina e prolactina no encéfalo: possível mecanismo de alterações metabólicas na gravidez
• Beneficiário: Vanessa Sayuri Nagaishi
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 12/02270-2 - Novos mecanismos celulares, moleculares e imunológicos das lesões renais agudas e crônicas: busca por novas estratégias terapêuticas
• Beneficiário: Niels Olsen Saraiva Câmara
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/00801-3 - Envolvimento dos neurônios Kiss1 na via neural através da qual o sistema circadiano regula o ciclo ovulatório
• Beneficiário: Regina Silva Paradela
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/12202-4 - Modulação das propriedades biofísicas de neurônios Kiss1 por fatores circadianos
• Beneficiário: Renata Frazão
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/15517-6 - Fatores moleculares envolvidos nas alterações metabólicas durante a gestação: papel do SOCS3
• Beneficiário: Thais Tessari Zampieri
• 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