title: High-fat diet obesity associated with insulin resistance increases cell proliferation, estrogen receptor, and PI3K proteins in rat ventral prostate.
abstract: 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 (ERβ) 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 ERβ 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 ERβ  and PI3K proteins. This change can facilitate the establishment of  proliferative lesions in rat prostate.
authors.affiliation: Sector Histology, Institute of Biomedical Sciences, Federal University of Uberlândia-UFU, Uberlândia, Minas Gerais, Brazil
authors.forename: Daniele Lisboa
authors.initials: DL
authors.lastname: Ribeiro
authors.forename: Maria Etelvina
authors.initials: ME
authors.lastname: Pinto
authors.forename: Alex
authors.initials: A
authors.lastname: Rafacho
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Bosqueiro
authors.forename: Samantha Yuri
authors.initials: SY
authors.lastname: Maeda
authors.forename: Janete Aparecida
authors.initials: JA
authors.lastname: Anselmo-Franci
authors.forename: Sebastião Roberto
authors.initials: SR
authors.lastname: Taboga
authors.forename: Rejane Maira
authors.initials: RM
authors.lastname: Góes
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism*; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D000077289:Letrozole; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000209:etiology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000209:etiology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D047629:Estrogen Receptor beta; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D009570:Nitriles; D011944:Receptors, Androgen; D014230:Triazoles; D013739:Testosterone; D000077289:Letrozole; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt