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Angiogenic, oxidative and hormonal responses of the prostatic microenvironment in high fat diet‐fed aging mice
Author(s) -
Cag Valeria Helena,
Almeida Lamas Celina,
Hermes Tulio,
Kido Larissa Akemi,
Minatel Elaine,
CollaresBuzato Carla,
Marostica Mario Roberto
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.899.4
Subject(s) - medicine , endocrinology , oxidative stress , angiogenesis , prostate , cancer
Aging and obesity are associated with prostatic lesion induction. Cellular proliferation, angiogenesis and oxidative stress could be altered in both processes. Thus, the aim of the study herein was to evaluate different molecules related to angiogenesis, oxidative stress and hormonal metabolism, considering aging and high‐fat diet intake on the mice prostate. FVB mice (30) were divided into the following groups: Young group (YNG ‐ 3 months old), Senile group (SE ‐ 11 months old), Senile and high‐fat diet (SHE ‐ 11 months old + high‐fat diet). YNG and SE groups received a normolipid diet (22% protein, 53% carbohydrate, 4.5% lipids and 2.9 Kcal/g) and SEH group, received a high‐fat and high‐calorie diet (20% protein, 50% carbohydrate, 21% lipids and 4.7 Kcal/g). After 60 days, the mice were anesthetized and the ventral prostate were collected and submitted to morphological analysis; and to immunohistochemical and immunoblotting evaluation for androgen and estrogen receptor (AR, ERα), vascular endothelial growth factor (VEGF), 4HNE and catalase. Weight gain, food and energy intake were analyzed. The results showed reduced weight gain and increased energy intake in SE group compared to YNG group. The high‐fat diet intake during aging led to increased weight gain and energy intake, despite diminishing food intake in relation to SE group. The prostatic morphology in SE group showed increased cellular proliferation, well‐differentiated adenocarcinoma, microacini, inflammatory cells and hypertrophied fibromuscular stroma. The high‐fat diet intake by aging mice aggravated the prostatic injuries in relation to SE group, showing increased cell proliferation, well‐differentiated adenocarcinoma, microacini and fibromuscular stroma hypertrophy. The inflammatory cell level was elevated in SHE group despite not significantly differing from SE group. In addition, reduced AR immunolabeling and increased ERα, VEGF, 4HNE and Catalase levels were verified in SE group as compared to YNG group. The high‐fat intake during aging led to an AR, ERα, VEGF, 4HNE and Catalase increase as compared to SE group. Thus, we concluded that the aging process led to harmful changes in the prostatic microenvironment, favoring glandular lesions. Also, the high‐fat intake in association with aging increased the microenvironment molecular imbalance, compromising glandular stromal‐epithelial interaction. The association of hormonal imbalance as well as angiogenic and oxidative processes due to aging and high‐fat diet intake dysregulated important signaling pathways in the prostate, particularly related to cell proliferation and inflammation, leading to pre‐malignant lesions. The glandular microenvironment ERα and angiogenic signaling stimuli, contributed to the glandular dynamic rupture. Support or Funding Information Sao Paulo Research Foundation (Fapesp‐2015 25714‐1