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Eliana H Akamine Departments of, Physiology and Biophysics, Pharmacology, Cell and Development of Biology, Department of Biological Sciences, Institute of Biomedical Sciences
Departments of, Physiology and Biophysics, Pharmacology, Cell and Development of Biology, Department of Biological Sciences, Institute of Biomedical Sciences

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Anderson C Marçal Departments of, Physiology and Biophysics, Pharmacology, Cell and Development of Biology, Department of Biological Sciences, Institute of Biomedical Sciences

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João Paulo Camporez Departments of, Physiology and Biophysics, Pharmacology, Cell and Development of Biology, Department of Biological Sciences, Institute of Biomedical Sciences

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Mara S Hoshida Departments of, Physiology and Biophysics, Pharmacology, Cell and Development of Biology, Department of Biological Sciences, Institute of Biomedical Sciences

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Luciana C Caperuto Departments of, Physiology and Biophysics, Pharmacology, Cell and Development of Biology, Department of Biological Sciences, Institute of Biomedical Sciences

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Estela Bevilacqua Departments of, Physiology and Biophysics, Pharmacology, Cell and Development of Biology, Department of Biological Sciences, Institute of Biomedical Sciences

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Carla R O Carvalho Departments of, Physiology and Biophysics, Pharmacology, Cell and Development of Biology, Department of Biological Sciences, Institute of Biomedical Sciences

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Besides the effects on peripheral energy homeostasis, insulin also has an important role in ovarian function. Obesity has a negative effect on fertility, and may play a role in the development of the polycystic ovary syndrome in susceptible women. Since insulin resistance in the ovary could contribute to the impairment of reproductive function in obese women, we evaluated insulin signaling in the ovary of high-fat diet-induced obese rats. Female Wistar rats were submitted to a high-fat diet for 120 or 180 days, and the insulin signaling pathway in the ovary was evaluated by immunoprecipitation and immunoblotting. At the end of the diet period, we observed insulin resistance, hyperinsulinemia, an increase in progesterone serum levels, an extended estrus cycle, and altered ovarian morphology in obese female rats. Moreover, in female obese rats treated for 120 days with the high-fat diet, the increase in progesterone levels occurred together with enhancement of LH levels. The ovary from high-fat-fed female rats showed a reduction in the insulin receptor substrate/phosphatidylinositol 3-kinase/AKT intracellular pathway, associated with an increase in FOXO3a, IL1B, and TNFα protein expression. These changes in the insulin signaling pathway may have a role in the infertile state associated with obesity.

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