Every day we are eating a variety of foods and our body needs to be able to assess what we are eating. Our body senses the quantity and quality of our food in order to get us to stop eating and to be able to direct the nutrients to the appropriate target tissues and metabolic pathways. Thus, differences in how we sense foods may profoundly affect our overall physiology and behavior. Obese and lean humans and other animals are known to respond differently to the same nutrients whether they are delivered directly into the gastrointestinal tract or eaten orally, as measured by changes in food intake, body weight and blood hormone levels. These differences may be accounted for by differences in intestinal morphology and function. The small intestine of obese humans and other animals is longer, has increased villi length/number and increased permeability compared with lean individuals. The mechanism underlying these differences is not known, but may be mediated by a direct action of nutrients on intestinal cells or secondary to the physiological alterations caused by obesity. Our lab is trying to delineate the contribution of diet and obesity by feeding laboratory rats different diets, inducing obesity through the use of these diets, and measuring changes in the morphology and function of the intestine. Results from these studies will not only help us to understand nutrient sensing in obese and lean individuals, but will give us a broader understanding of the mechanisms responsible for nutrient-driven cellular adaption in the intestine and in finding a therapy for intestinal disorders that include Crohn’s disease, irritable bowel syndrome and cancer.