The physiological mechanism by which ingested fats terminate eating in animals and humans is unknown. This proposal is designed: (1) to elucidate the critical stimuli for fat-induced postprandial satiety; (2) to determine the site of action for such stimuli; and (3) to examine the neural, endocrine or neuroendocrine mechanisms involved in mediating this satiety response in Sprague Dawley rats. Knowlege of such mechanisms are likely to be of major importance for developing effective treatments for the control of eating disorders, such as obesity and bulimia. There is evidence that genetically obese animals and humans are less responsive to the satiating effects of fats. Therefore, a secondary aim of this proposal is to examine differences in fat-induced satiety between lean and genetically obese rats. To determine the critical stimuli involved in fat-induced satiety, tests will be carried out with specific short-, medium-, long-, and very long-chain fats. These substances will be assayed for their effects on satiety by infusing them directly into stomach or duodenum of rats feeding normally or sham feeding. The site of action for inducing satiety will be determined by measuring triglyceride levels in the blood subsequent to infusions, infusing fats into the hepatic-portal vein or the inferior vena cava, on confing fats in the stomach, of sham and real feeding rats. Experiments to determine the neural and/or hormal mechanisms that mediate those fat stimuli determined to be most effective for inducing satiety are also proposed. Total subdiaphragmatic vagotomy, selective vagotomies, selective afferent and efferent vagotomy and spinal visceral disconnection will be used to analyze neural mechanisms mediating fat-induced satiety. Measurement of peptides and the use of selective peptide antagonists will be used to assess the involvement of intestinal hormones in mediating the satiating response to those fats that are the most potent stimuli for inducing satiety. The specificity of fats for inhibition of various oral stimuli will be assessed. Those fat stimuli that are most effective for inducing satiety and those mechanisms that are found to mediate the satiety response in Sprague Dawley rats will be subsequently tested in identical paradigms in lean and obese Zucker rats.
