High-fat diet-induced adipokine and cytokine alterations promote the progression of prostate cancer in vivo and in vitro.

Abstract

High-fat diet (HFD) -induced obesity is associated with more aggressive and lethal prostate cancer (PCa) in males, although the exact underlying mechanisms remain unclear. In the present study, transgenic adenocarcinoma of mouse prostate (TRAMP) models fed on an HFD (40% fat) or a control diet (CD; 16% fat) were generated, and cancer differentiation, local invasion and metastasis were compared at 20, 24 and 28 weeks. Mouse sera from each group were collected, and adipokines and cytokines were measured using multiplex immunoassays. HFD-sera and CD-sera were additionally processed into conditioned media (2.5% mixed sera), and in vitro studies were conducted to determine the proliferation, migration and invasion of cancer cells when conditioned media were used for culture. In TRAMP mice, HFD feeding increased body weight and adipose tissue deposition, and promoted the progression of PCa, specifically with regard to poorer differentiation, increased local invasion and metastasis rate. Sera from HFD-fed TRAMP mice contained increased levels of leptin, and a time-dependent increasing trend in the levels of CC chemokine ligand (CCL)3, CCL4, CCL5 and CXC chemokine ligand (CXCL)10 was observed. However, no alterations were detected in the levels of adiponectin, interleukin (IL)-4, IL-5, IL-6, IL-12p70, interferon-γ, tumor necrosis factor-α, CCL2, CCL7, CCL11, CXCL1 and CXCL2. In vitro studies determined that HFD-sera-conditioned medium promoted proliferation, migration and invasion of DU145 cells, as compared with CD-sera-conditioned medium and serum-free medium. In conclusion, the results of the present study suggested that the circulating adipokine and cytokine alterations in response to excess adipose tissue deposition induced by HFD feeding contributed to PCa progression.