Abstract 4437: Dysregulated lipid metabolism and high-fat diet influences prostate cancer (PCa) progression

Abstract Dysregulation of lipid metabolism is observed during the development and progression of various types of cancer including prostate cancer (PCa). Systemic metabolic changes driven by genetic alterations in conjunction with obesity and a high-fat diet have been demonstrated to induce PCa progression. In this study, we aimed to investigate the impact of high- and low-fat diets on the progression and morbidity of prostate cancer, utilizing inducible genetically engineered mouse models (GEMMs) that mimic different grades of prostate cancer. The mice were initially placed on a standard diet until week 6, after which they were randomly assigned to either a low-fat or high-fat diet. At week 8, the Cre recombinase enzyme was activated to induce the desired phenotype in the GEMMs, effectively mimicking the initiation and progression of prostate cancer. The experimental design allowed us to gain insights into the interplay between dysregulated lipid metabolism, diet, and the pathogenesis of prostate cancer. Two groups of mice were taken for the study, with one group being fed a low-fat diet and the other group being fed a high-fat diet. The mice were maintained on their respective diets for a period of 1, 3, and 5 months. At each endpoint, tissue samples were collected. Samples were taken from the prostate, plasma, and liver tissues. These samples were then subjected to various analyses to investigate the changes occurring at the molecular and cellular level. Blood was collected to determine lipidomic content in response to high and low-fat diet and the relation of tumour progression. Finally, faecal samples were collected throughout the duration of the experiment to perform metagenomic studies. The consumption of a high-fat diet significantly increased the body weight of the mice which corresponded to increased liver weight. Furthermore, we identified that the consumption of a high-fat diet significantly correlated with an increase in prostate weight at 3 and 5 months after initiation. Preliminary metabolomic analysis of the plasma revealed a distinct clustering of samples based on the consumed diet. Metagenomic analyses conducted at 1 and 3 months indicated a visible shift in the composition and diversity of gut microbiota in mice fed either a high- or low-fat diet. In conclusion, our study will shed light on the influence of dietary factors on prostate cancer development, providing valuable information for the development of targeted therapeutic strategies to combat this disease. Citation Format: Saurav Subedi, Federico La Manna, Katja Ovchinnikova, Eugenio Zoni, Nicola Zamboni, Bahtiyar Yilmaz, George N. Thalmann, Marianna Kruithof-de Julio. Dysregulated lipid metabolism and high-fat diet influences prostate cancer (PCa) progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4437.