High-Fat Diet Obesity Associated With Insulin Resistance Increases Cell Proliferation, Estrogen Receptor, and PI3K Proteins in Rat Ventral Prostate

Autor(es)

Ribeiro, Daniele Lisboa ^{[1, 2]} ; Pinto, Maria Etelvina ^[1] ; Rafacho, Alex ^[3] ; Bosqueiro, Jose Roberto ^[4] ; Maeda, Samantha Yuri ^[1] ; Anselmo-Franci, Janete Aparecida ^[5] ; Taboga, Sebastiao Roberto ^[1] ; Goes, Rejane Maira ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista UNESP, Inst Biosci Letters & Exact Sci, Dept Biol, Sao Paulo - Brazil

^[2] Univ Fed Uberlandia, Inst Biomed Sci, Sect Histol, BR-38400 Uberlandia, MG - Brazil

^[3] Univ Estadual Paulista UNESP, Sch Sci, Dept Phys Educ, Sao Paulo - Brazil

^[4] Univ Fed Santa Catarina, Ctr Biol Sci, Dept Physiol Sci, Florianopolis, SC - Brazil

^[5] Univ Sao Paulo, Sch Dent, Dept Morphol Stomatol & Physiol, BR-09500900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Andrology; v. 33, n. 5, p. 854-865, SEP-OCT 2012.
• Citações Web of Science: 23

Resumo

In this study, we evaluated the effects of obesity and insulin resistance induced by a high-fat diet on prostate morphophysiology, focusing on cell proliferation, expression of androgen (AR) and estrogen receptors (ER) and proteins of the insulin signaling pathway. Adult male Wistar rats were fed a high-fat diet (20% fat) for 15 weeks, whereas control animals received a balanced diet (4% fat). Both groups were then divided and treated for 2 weeks with 1 mg/kg body weight/day of the aromatase inhibitor letrozole or vehicle only. The ventral prostate was analyzed with immunohistochemical, histopathological, stereological, and Western blotting methods. Obese rats showed insulin resistance, hyperinsulinemia, and reduced plasma testosterone levels. The incidence of prostatic intraepithelial neoplasia (PIN) was 2.7 times higher in obese rats and affected 0.4% of the gland compared with 0.1% PIN areas found in control rats. Obesity doubled cell proliferation in both prostate epithelium and stroma. AR content decreased in the prostate of obese rats and estrogen receptor beta (ER beta) increased in this group. Protein levels of insulin receptor substrate 1 and protein kinase B diminished in the obese group, whereas phosphatidylinositol 3-kinase (PI3K) increased significantly. Most structural changes observed in the prostate of obese rats normalized after letrozole treatment, except for increased stromal cell proliferation and ER beta expression, which might be associated with insulin resistance. This experimental model of obesity and insulin resistance induced by a high-fat diet increases cell proliferation in rat prostate. Such alterations are associated with decreased levels of AR and increased ER beta and PI3K proteins. This change can facilitate the establishment of proliferative lesions in rat prostate. (AU)

• Processo FAPESP: 08/00542-0 - Repercussões da obesidade na próstata ventral de ratos: caracterização histológica e análise do papel estrogênico
• Beneficiário: Daniele Lisboa Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/05078-2 - Repercussões da obesidade na próstata ventral de ratos: caracterização histológica e análise do papel estrogênico
• Beneficiário: Samantha Yuri Maeda
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 08/05341-2 - Repercussões da obesidade na próstata ventral de ratos: caracterização histológica e análise do papel estrogênico
• Beneficiário: Rejane Maira Góes
• Modalidade de apoio: Auxílio à Pesquisa - Regular