Project Number: 3062-51000-050-00-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2014
End Date: Sep 30, 2019
Objective 1 - Determine whether obesity-related impairment of selenium-antitumori-genesis in appropriate animal models is due to adiposity, energy imbalance or excess dietary fat. Sub-objective 1.A: Determine whether reduction of Se-antitumorigenesis by a high-fat diet depends on development of adiposity. Sub-objective 1.B: Determine the metabolic basis for the effect of obesity in reducing the antitumorigenic effects of dietary Se. Objective 2 - Examine the effect of high selenium status on the diabetogenic effect of obesity, including effects on glucose metabolism. Also examine the influence of obesity and its metabolic consequences on selenium metabolism. Sub-objective 2.A: Determine whether high Se status is related to increased risk of type 2 diabetes risk. Sub-objective 2.B. Determine whether obesity affects Se metabolism. Objective 3 - Study the influences of selenium and obesity and their interaction on colonic microbiota and its metabolites that may improve health. Sub-objective 3.A: Determine whether Se promotes a hindgut microbiota that produces metabolites beneficial to the host. Sub-Objective 3.B: Determine the role of gut microbiota in colonic Se-antitumorigenesis.
This project builds upon the work of our last project by addressing the interaction of the cancer-preventive effects of dietary selenium (Se) and the cancer-promoting effects of obesity. The anticarcinogenic potential of Se has been established in hundreds of studies with animal/cell models; however, clinical trial results have been inconsistent. It is likely that obesity contributed to that inconsistency. Many subjects in the most recent, and largest, relevant clinical trial were overweight/obese, and obesity is a known cancer risk factor, enhancing each stage of carcinogenesis through mechanisms inhibitable by dietary Se. At the same time, high Se status has been associated with increased risk to type 2 diabetes (T2D). These associations involving risk (rather than causality), raises two questions relevant to understanding the health value of Se-containing foods: Who can benefit from increased Se intake? Who may be at risk from increased Se intake? This project takes innovative approaches in addressing these questions in the context of the effects of obesity. Objective 1 will determine whether obesity-related impairment of Se-antitumorigenesis is due to adiposity, energy imbalance or excess dietary fat. Objective 2 will examine the effect of high Se status on the diabetogenic effect of obesity, and the influence of the metabolic features of obesity on Se metabolism. Objective 3 will determine the effects of Se and obesity on the colonic microbiota, which has relevance to colon cancer, dietary energy extraction, and immunity. This project comprises the first multidisciplinary studies of obesity-Se interactions relevant to cancer prevention and diabetes. Results will show whether obese individuals are likely to benefit from dietary Se.