Ingestion of high fat diets is associated with serious public health problems, such as coronary heart disease, hypertension, non-insulin dependent diabetes mellitus, some cancers, and obesity. Numerous reports suggest that elevated intake of dietary fat, rather than total energy consumption, promotes weight gain. In order to effectively control intake of fatty foods, the physiological mechanisms which limit fat intake must be understood. This proposal is to identify these mechanisms in Sprague Dawley rats, and in three genetic models of obesity characterized by abnormal fat intake: Zucker fa/fa, Osborne Mendel and S 5B/PI rats. Experiments are proposed in Sprague-Dawley rats to determine to what extent physiological stimulation of the intestine by fats occurs during normal feeding and what effect such as stimulation has on meal size. This will be accomplished by: (1) Determining the gastric emptying rates and the compositions of the various lipid moieties that enter the intestine when fats of different chain lengths and degrees of saturation are ingested. Most experiments employ the sham feeding procedure to gain complete control of intestinal food stimuli; Each of the phenomena determined in the sham feeding model will be validated in tests of real feeding rats by: (2) examining mechanisms that are involved in the control of meal size by physiologically appropriate intestinal fat infusions and determine if these effects are specific to satiety by use of conditioned taste aversion paradigms; (3) determine if vagal and CCK mechanisms mediate intestinal satiety elicited by physiologically appropriate stimuli; (4) determine the brain regions involved In mediating the intestinal control of meal size by use of c-Fos immuno-histochemistry and selective brain lesions. This proposal also seeks to (5) determine the interaction of oral and Intestinal fat stimuli in the control of meal size. (6) These issues will also be explored in genetically obese Zucker, Osborne-Mendel and S 5B/pl rats. The effects of all experimental treatments involved with ingestion will be measured by both interval intakes and by microstructural analysis of electronic lickometer records that permit 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 during fat meals. The studies with the genetic models may provide a link between recent molecular biological advances and also provide potential pharmacological targets for new treatments of obesity and of the binge eating that occurs in bulimia.
