Obesity is a major medical problem in the United States. A National Institute of Health Consensus Panel on health implications of obesity has declared obesity a disease (Kolata, 1985). This was based on a number of studies that showed that the obese are prone to a wide variety of disorders including hypertension, adult onset diabetes, hypercholesterolemia, hypertriglyceridemia, heart disease, some forms of cancer, gall stones, arthritis and gout. In animal studies the single most effective way to increase life expectancy is reduction of body fat. While there is good evidence to lose weight, most approaches for weight loss do not result in long term weight success. This failure is based on the lack of understanding of the basic mechanisms of regulation of adipose tissue development. Genetic predisposition to obesity is well established by the studies of adopted twins. The genetically obese pig is a model that displays many of the adipose tissue developmental patterns seen in obese humans (see appendix). Development of adipose tissue in utero involves events associated with cell division and differentiation. These early developmental changes can be closely followed in simple systems which employ in vitro cell culture procedures. In utero, a more complex system is involved, and many factors act in concert to regulate adipose cell development. To identify those factors in utero which have an impact on adipogenesis, it is necessary to characterize normal adipose cell development and the response of tissue to manipulation of this complex system. The endocrinology of adipogenesis will be characterized prenatally. The developmental aspects of adipogenesis in vivo and in vitro will be monitored using histochemical and biochemical techniques. The first series of experiments will test the hypothesis that an altered adipocyte conversion rate or an abnormal adipocyte metabolism in the fetal animal is responsible for genetic obesity. The use of the genetically obese pig models permits a range of studies in the pre- obese fetal animal that are impossible to do in any other species. The second series of experiments will examine the endocrine requirements for fetal adipocyte proliferation and differentiation in vivo and in vitro. The hypothalamic-pituitary axis will be examined as a source of adipogenic factors in the last series of experiments. These studies will lead to identification of specific factors that cause adipocyte abnormalities in the obese condition.
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