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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Endocrinology; v. 155, n. 11, p. 4226-4236, NOV 2014.
Web of Science Citations: 16
Abstract

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)

FAPESP's process: 13/00801-3 - Involvement of Kiss1 neurons in the neural pathway through which the circadian system regulates the ovulatory cycle
Grantee:Regina Silva Paradela
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 10/18086-0 - Molecular basis of leptin resistance
Grantee:Jose Donato Junior
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 12/12202-4 - Kiss1 neurons biophysical properties modulation by circadian factors
Grantee:Renata Frazão
Support Opportunities: Regular Research Grants
FAPESP's process: 13/16374-7 - Crosstalk between leptin and prolactin in the brain: possible mechanism of metabolic changes during pregnancy
Grantee:Vanessa Sayuri Nagaishi
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
Grantee:Niels Olsen Saraiva Câmara
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 12/15517-6 - Involvment of molecular factors in metabolic changes during pregnancy: role of SOCS3
Grantee:Thais Tessari Zampieri
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/21722-4 - Mechanism of action of bromocriptine and prolactin antagonists in the treatment of Diabetes and Obesity
Grantee:Isadora Clivatti Furigo
Support Opportunities: Scholarships in Brazil - Doctorate