Abstract SY28-02: The adipose-cancer link: From microenvironment to metabolomics

Abstract

Abstract This presentation will showcase the interface of systemic and localized disturbances in metabolism with tumor development, specifically focusing on colorectal cancer. Colorectal cancer is the second leading cause of cancer-related death worldwide among both men and women. Risk and preventive factors are well established and include, among others, lack of physical activity and obesity (risk) as well as aspirin use and screening (prevention). Adipose tissue is emerging as a key player in carcinogenesis through the secretion of proinflammatory cytokines and adipokines. The colon is surrounded by adipose tissue, which supports the direct (paracrine) adipose-colon crosstalk and influence as a tumor microenvironment, as well as systemic influences on colon carcinogenesis factors secreted into the bloodstream. As part of the ColoCare cohort, an international, multicenter cohort of colorectal cancer patients, we have investigated adipose tissue distribution, composition, characteristics, and possible influence on colorectal tumors. In an integrated analysis of the transcriptome and metabolome of visceral and subcutaneous adipose tissue (VAT and SAT, respectively), we showed that there are distinct differences that may play a central role in driving carcinogenesis (1). These analyses are ongoing and have been extended to blood-based measures of the inflammasome and metabolome, as well as tumor characteristics. Adipose tissue biology can also be directly affected by weight-loss interventions through diet and exercise. As part of the Nutrition and Exercise in Women (NEW) study, we showed that weight loss results in changes in adipose tissue gene expression as well as corresponding reductions in biomarkers, including inflammatory biomarkers (2, 3).