Obesity induced by high-fat diet promotes insulin resistance in the ovary

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 TNF alpha protein expression. These changes in the insulin signaling pathway may have a role in the infertile state associated with obesity. Journal of Endocrinology (2010) 206, 65-74Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)EHAUniv São Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 São Paulo, BrazilUniv São Paulo, Dept Cell & Dev Biol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, BR-04023900 Diadema, SP, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, BR-04023900 Diadema, SP, BrazilFAPESP: 2006/52163-7FAPESP: 2006/60215-7CNPq: 477906/2006-0Web of Scienc