Inhibition of Fatty Acid-Binding Protein 4 Limits High-Fat-Diet-Associated Prostate Tumorigenesis and Progression in TRAMP Mice.

Fatty acid-binding protein 4 (FABP4) is an important adipokine associated with inflammatory responses and metabolic regulation. Although a high-fat diet (HF) and/or HF-mediated obesity have been clearly linked to the progression of prostate cancer, with FABP4 potentially playing a critical role in this relationship, the mechanisms by which FABP4 facilitates this interaction remain unclear. After generating FABP4 knockout (FABP4) transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, it was found that FABP4 TRAMP mice presented significantly ameliorated prostate tumorigenesis and tumor progression along with decreased body weight, protumorigenic cytokine secretion, and pan-amino acid synthesis when compared to TRAMP mice under the HF condition. Additionally, treatment with BMS309403-a chemical inhibitor of FABP4-was observed to abrogate the HF-mediated TRAMP tumor progression, along with reductions in body weight and cytokine production. Thus, FABP4 plays an essential role in the progression of HF-mediated prostate cancer through the modulation of metabolic and inflammatory pathways, providing a potential therapeutic target for prostate cancer.