Department of Physiology and Biophysics, University of São Paulo, São Paulo/SP, Brazil.
J Endocrinol. 2010 Jul;206(1):65-74. doi: 10.1677/JOE-09-0461. Epub 2010 May 7.
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 TNFalpha protein expression. These changes in the insulin signaling pathway may have a role in the infertile state associated with obesity.
除了对周围能量稳态的影响外，胰岛素在卵巢功能中也起着重要作用。肥胖对生育能力有负面影响，并且可能在易患多囊卵巢综合征的女性中发挥作用。由于卵巢胰岛素抵抗可能导致肥胖女性生殖功能受损，因此我们评估了高脂肪饮食诱导肥胖大鼠卵巢中的胰岛素信号通路。雌性 Wistar 大鼠接受高脂肪饮食 120 或 180 天，并通过免疫沉淀和免疫印迹评估卵巢中的胰岛素信号通路。在饮食期末，我们观察到肥胖雌性大鼠出现胰岛素抵抗、高胰岛素血症、孕激素血清水平升高、发情周期延长和卵巢形态改变。此外，在接受高脂肪饮食治疗 120 天的肥胖雌性大鼠中，孕激素水平升高伴随着 LH 水平的升高。高脂肪喂养的雌性大鼠的卵巢中胰岛素受体底物/磷酸肌醇 3-激酶/AKT 细胞内途径减少，与 FOXO3a、IL1B 和 TNFalpha 蛋白表达增加有关。胰岛素信号通路的这些变化可能与肥胖相关的不孕状态有关。
