Description
The overall goals of the research conducted by the members of the Diet, Energy Balance & Environmental Disease Risk Research Focus Area (RFA3) are to elucidate the interactions of nutrition, genetics and exposure to environmental toxicants with respect to the etiology and progression of human disease processes. One area of emphasis will be characterizing (including elucidating the underlying mechanisms) the impact of energy balance modulation such as calorie restriction, diet-induced obesity, and physical activity, on carcinogenesis caused by physical and chemical environmental carcinogens, with a particular focus on the role of the IGF-1 pathway. A second area of emphasis will be elucidating the mechanisms by which specific dietary components affect the carcinogenesis process. This will be accomplished through the development and use of animal models in preclinical mechanism-driven and prevention studies that will ultimately inform epidemiologic studies and lead to clinical trials . A third area of emphasis will be the use and development of animal models to identify and verify new targets for prevention of environmentally-related diseases, including the IGF-1/Akt signaling pathway and the signaling pathways activated by prostaglandins.
The Specific Aims of Research Focus Area 3 are:
- To use animals exposed to detrimental environmental agents found in the human environment in prevention/intervention studies employing specific dietary modifications;
- To use animals with genetic modifications that occur in humans as a result of exposure to environmental agents for studies on the mechanisms of modification of health outcomes through the use of specific dietary components and/or energy balance alterations; and
- To develop new animal models of human disease for use in the above prevention/intervention studies.
These objectives will be achieved through interdisciplinary interactions between members of this RFA and through interactions with members of other RFAs.
Research Significance
Exposure to environmental agents, either physical or chemical, can lead to the development of many different diseases. While removal of these agents from our environment would be an ideal and primary preventive action, this is usually not feasible or practical. However, a secondary line of defense for preventing environmental agent-induced pathologies is to intervene and reverse early events associated with the disease process. As more of the physiological processes and molecular pathways that are perturbed by environmental toxicants are identified, additional targets for prevention/intervention are made available. Toxicants of various types are important contributors to the risk of cancer and other diseases. Many human diseases, including cancer, are also affected by the interaction of genetic susceptibility and environmental exposures. Nutrition, as a determinant of growth and body composition, also influences cancer risk, directly due to carcinogens in food or indirectly by the hormonal and metabolic responses of the body to growth and obesity. There is strong evidence that rapid growth and obesity enhances the risk of several chronic diseases including cancer, diabetes and hypertension. Particularly alarming are the increasing rates of obesity among children and adolescents, portending further increases in the rates of adult obesity and obesity-related diseases. The mechanisms underlying the relationship between obesity and disease are not well understood; research in this area is urgently needed to facilitate the development of new prevention strategies for cancer and other diseases.
A number of dietary studies in mice using calorie restriction and diet-induced obesity show reduced or elevated serum levels of IGF-1, respectively. The relationship between elevated serum levels of IGF-1 and the risk of lung, bladder, colon, prostate and breast cancer has been suggested in human studies. There is a need to further clarify this relationship and to understand the mechanisms by which IGF-1 is regulated by energy balance, as well as bioactive food components. This is important because ongoing animal studies suggest that serum IGF-1 levels significantly impact the response to environmental carcinogens.
The development of effective chronic disease preventive interventions is being enhanced through the use of relevant animal models to refine and extend potential leads from clinical and epidemiological studies. In particular, genetically altered mice, with modifications of specific disease-related genes, are providing powerful tools for studying the ability of specific nutrients or particular dietary regimens, including energy balance interventions, to enhance or repress the progress of the disease. An understanding of which nutritional and/or energy balance modifications are beneficial in animal models should lead to population and clinical intervention studies in humans.
All the members of RFA3 share an interest in diet as a modifier of environmentally induced disease, particularly cancer. Several members are investigating the relationship between obesity, IGF-1 and cancer susceptibility (DiGiovanni, Hursting, Fuchs-Young, Johanning). Other members are studying IGF-1 signaling through PI3K/Akt as potential targets for prevention of several types of cancer (DiGiovanni, Fischer). In addition, the impact of specific dietary components, e.g., vitamins A and E, phytochemicals and fatty acids on carcinogenesis are under investigation (Kline, Sanders, Lane, Ciolino, Fischer). A wide range of experimental approaches are being used by RFA3 members, from molecular in vitro studies to the development of animal models to identify new targets for prevention and to test the efficacy of dietary interventions. The long-term goal is to develop new diet-related strategies in humans that minimize the health impact of a variety of environmental toxicants.
Members
Fischer, Susan Carcinogenesis, SPRD
Ciolino, Henry Nutritional Sciences, UT Austin
DiGiovanni, John Carcinogenesis, SPRD
Fuchs-Young, Robin Carcinogenesis, SPRD
Hursting, Stephen Nutritional Sciences, UT Austin
Johanning, Gary Veterinary Resources, Bastrop
Kline, Kimberly Nutritional Sciences, UT Austin
Lane, Michelle Nutritional Sciences, UT Austin
Sanders, Bob Molecular Genetics & Microbiology , UT Austin
