Anti-inflammatory Dietary Compounds, Wnt Pathway and the Prevention of Obesity Associated Colorectal Cancer

Mounting epidemiological and experimental evidence consistently indicates that obesity is a robust risk factor for several common cancers, and especially so for colorectal cancer. As obesity has reached an epidemic level and increases in the scope of the problem are further projected, it is critical to understand the mechanism(s) responsible for the link and thereby to develop strategies for prevent obesity-related cancer. My prior seminal work shows that diet-induced obesity induces chronic inflammation in the mouse colon, indicated by the elevation of inflammatory cytokines with TNF-a in particular, and accompanying this elevated inflammation is the up-regulation of several key components of the Wnt signaling, a critical pathway responsible for colon cancer. Based on these findings, the aim of the current project is to explore dietary strategies to attenuate obesity-associated colonic inflammation, and thereby to suppress Wnt-signaling and determine the degree to which the most effective bioactive component identified by the previous cell culture study will be in synergy with vitamin D to diminish obesity-elevated Wnt-signaling in vivo and the subsequent intestinal tumorigenesis. With the successful completion of the project, we expect to have determined a novel mechanism involved in the chemopreventive effects of these compounds. Importantly, we expect to have established a novel and potentially more valuable dietary approach to prevent obesity-associated cancer, since a long-term pharmaceutical application is not practical for this chronic disease given side-effects normally associated with chemical drugs. Advances in this regard will help address the need to further the goal of agricultural research nationally and in Massachusetts to improve public health, particularly with the consideration of the prevalence of obesity.