Maternal High-Fat Diet Promotes the Development and Progression of Prostate Cancer in Transgenic Adenocarcinoma Mouse Prostate Offspring
2018
Tian Yang | Xiaobo Wu | Jimeng Hu | Mengbo Hu | Hua Xu | Haowen Jiang | Qiang Ding
Background/Aims: We aim to investigate the impact of maternal high fat diet (HFD) on the development and progression of prostate cancer (PCa) in transgenic adenocarcinoma mouse prostate (TRAMP) offspring. Methods: The TRAMP model was used, and divided into maternal HFD group and normal diet (ND) group in the present study. Each group contained 36 TRAMP mice. Serum levels of leptin, adiponectin, interleukin (IL) -1α, IL-1β, IL-6, tumor necrosis factor-α and monocyte chemotactic protein-1 were measured by the 20th, 24th and 28th week old through ProcartaPlex Multiplex Immunoassay. Body fat ratio was measured by MiniQMR. Tumor formation rate was measured through hematoxylin and eosin (H&E) staining, and mortality rate was measured meantime. Western blot was applied to determine the levels of Protein Kinase B (Akt) and Phosphatase and tensin homolog (PTEN). Results: The mortality rate of maternal HFD group was significantly higher than that of ND group (P = 0.046). The tumor formation rate was significantly higher in maternal HFD group than in ND group only in 20th week subgroup (P = 0.040). A significant increase of leptin was seen in maternal HFD 20th and 24th week subgroups (P = 0.001 and < 0.001, respectively) and a decrease of adiponectin was seen in maternal HFD 20th and 28th week subgroups (P =0.006 and < 0.001, respectively). Besides, an activated phos-Akt (P-Akt) and deactivated PTEN were observed in maternal HFD group. Conclusions: Maternal HFD could increase the standard serum leptin level, inhibit the expression of PTEN protein, promote P-Akt protein expression, activate the PI3K/Akt pathway, and ultimately promote the development and progression of PCa in TRAMP offspring.
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