Ingestion of high fat diets is associated with serious public health problems, such as coronary heart disease, hypertension, non-insulin dependent diabetes mellitus, and obesity. In order to effectively control intake of fatty foods, the physiological mechanisms which limit fat intake must be understood. But at present, the mechanisms by which fats produce satiation in humans and animals are largely unknown. This proposal is designed to identify these mechanisms in Sprague Dawley rats and in lean and genetically obese Zucker rats, a rodent model of obesity characterized by high intake of fat. Experiments are proposed: (1) to determine the site of action for the short-term, preabsorptive satiating effect of fats by comparing the satiating potency of fats of different chain lengths and degrees of saturation when fat stimuli are limited to: (a) the lower intestine, (b) the upper small intestine or (c) the stomach; (2) to determine if the vagally mediated component of the satiety effect of fats depends upon afferent or efferent vagal fibers in Sprague-Dawley rats and determine if vagal pathways for fat-induced satiety operate normally in lean and genetically obese Zucker rats; (3) to determine if the vagal and CCK mechanisms involved in the preabsorptive satiating effect of fats are additive; (4) to determine if there are sex differences in the preabsorptive satiating effect of fats and if such differences exist, then determine the role of gonadal hormones in the observed differences in Sprague-Dawley and Zucker rats; and (5) to determine the effects of adrenalectomy, glucocorticoid or mineralocorticoid replacement, and corticotropin releasing factor in Zucker rats on the preabsorptive satiating effect of fats. The effects of all experimental treatments will be measured by both interval intakes and by microstructural analysis of electronic lickometer records that permits estimates of the moment-by-moment interaction of the positive (stimulating) and negative (satiating) feedback effects of ingested food and specific treatments during a meal. The results of these studies will provide fundamental information about the biological mechanisms that control fat intake. The results may also provide potential pharmacological targets for new treatments of the binge eating that occurs in bulimia and some forms of obesity, particularly among women.
