Development of a dynamic model for the regulation of appetite

Abstract

Satiety arises through the function of the gastrointestinal tract. Satiety increases through the distension of the stomach volume, and the absorption of nutrients in the small intestines. In the small intestines there exists systems that detect the energy content, and the type of nutrients. This mediates a feeling of satiety through various endocrine systems. In this master's thesis the regulation of Cholecystokinin (CCK) was focused upon, but other mediators of satiety and hunger that should be considered in further studies are glucagon-like peptude 1 (GLP-1), polypeptide YY (PYY) and Ghrelin.A dynamical model for the behavior of circulating levels of the appetite reducing hormone Cholecystokinin (CCK) was derived. A model for changes in gastric content volume is also proposed. Meal satiety is indirectly modeled through the changes in gastric content volume (GCV), and through the change in the circulating levels of CCK. Gastric distension is assumed to be an acute mediator of satiety, while CCK is an indirect measure of nutrients delivered to the small intestines. The inputs to the model are the initial volume and the initial caloric content.The GCV model was developed by generalizing a three parameter linear exponential model proposed by Goetze et. al. [2005] through the use of studies in litterature with an intragastric infusion of a multinutrient liquid meal, where the caloric ration of 41.5% carbohydrate, 41.2% fat and 17.3% protein. The time span of this model is from zero to sixty minutes after a liquid meal. The volume of the meal ranges from 200ml to 600ml, and the energy content ranges from 200 to 400 kcal.The dynamical model for the circulating blood levels of CCK is developed using a proposed negative feedback regulation. The parameters in this model is estimated by using data from several studies with intraduodenal infusion of solution consisting predominately of long-chain triglycerides (soyabean extract). The input to this model is an estimation of the caloric load delivered from the stomach by gastric emptying. The caloric load of the studies used were between 0.25-4 kcal/min.