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

## TL;DR

Blocking FABP4 reduces prostate cancer progression in mice fed a high-fat diet by affecting metabolism and inflammation.

## Contribution

This study identifies FABP4 as a key mediator in high-fat-diet-driven prostate cancer progression and validates it as a therapeutic target.

## Key findings

- FABP4 knockout TRAMP mice showed reduced prostate tumor progression and lower body weight on a high-fat diet.
- Inhibiting FABP4 with BMS309403 reduced tumor progression and cytokine production in high-fat-fed TRAMP mice.
- FABP4 modulates metabolic and inflammatory pathways to influence prostate cancer progression.

## Abstract

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.