Early Environmental Contributions to Adult Onset Obesity

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DESCRIPTION (provided by applicant): Metabolic diseases, such as obesity and type II diabetes, are symptomatic illnesses of modern American society and obesity alone currently accrues $96 billion of direct health costs per year. Within 5 years, a third of adults in the US will be obese. While genotypes clearly contribute to the predisposition for obesity, it is the environment that determines its manifestation. Fetal environment is a critical factor for common adult diseases in humans, such as heart disease, high blood pressure, type II diabetes, and obesity. Animals produced through the use of assisted reproductive technology are susceptible to obesity in adulthood. Over a million people, since 1995, have been conceived using some form of assisted reproductive technology. Although few of these people have reached adulthood presently, most show signs of clinical obesity. The in vitro culture environment is known to alter the energy metabolism of oocytes and embryos in animals, as well as humans. The long-term goal of this proposed study is to determine how the in vitro culture environment affects homeostatic systems that lead to adulthood obesity. Most studies to date of metabolic disease alter the environment of the pregnant adult female. This study is innovative in that the early developmental environment will be controlled by using in vitro maturation and in vitro fertilization techniques; thereby allowing investigation of environmental influence on the early embryo, and the subsequent effects on the resulting adult animal. Although the constituents in culture media leading to obesity are not known, alcohol is one common component used in many assisted reproductive technology procedures. Results from our laboratory suggest that mice specifically exposed to ethyl alcohol during in vitro maturation of oocytes gradually become obese in adulthood. To pinpoint which physiological systems are involved in this adult-onset obesity, a comprehensive cage metabolic monitoring system, as well as changes in gene expression will be used to identify the alternations in energy regulation of mice exposed to alcohol as compared to controls. These experiments will help to elucidate the systems and pathways which are established within the early maternal and embryonic environment that influence a predisposition to adulthood diseases, such as obesity and type II diabetes.