Understanding gastro intestinal regulation of appetite drives offer a view on a therapeutic window for obesity which promises better clinical benefits as well as lower side effects. Bariatric surgery is a good model to investigate appetite reduction in humans and rodents, because it provides major changes in appetite with subsequent weight loss maintenance. Gastric bypass, but not gastric banding cause increased postprandial PYY and GLP-1 favouring enhanced satiety. An early and exaggerated insulin response mediates improved glycaemic control. The rodent model of bypass show elevated PYY, GLP-1 and gut hypertrophy compared with sham-operated rats. Moreover, exogenous PYY reduced food intake while blockade of endogenous PYY increased food intake. A prospective follow-up human study of gastric bypass showed progressively increasing PYY, oxyntomodulin, and GLP-1 responses associated with enhanced satiety. Blocking these responses in animal and human models leads to increased food intake. A paradoxical increase in energy expenditure after gastric bypass secondary to the enhanced postprandial energy expenditure is evident in both humans and rodents.
Changes occur in the sensory, reward and physiological domains of taste that may mechanistically contribute to the alterations in food preferences after gastric bypass. The sustained nature of weight loss, reduced appetite and shifts in food preferences may be explained by gut adaptation and chronic hormone elevation, especially as blockade of the gut hormones result in enhanced appetitive behaviour.
Glycaemic control improves rapidly and is a result of several mechanisms including reduction in calorie intake, weight, hepatic and peripheral insulin resistance as well as an enhanced insulin secretion. Significantly altered gut hormones, bile acid metabolism and gut microbiota alterations have been implicated. Finally the improved metabolic milieu results in end organ damage reversal in some patients.
Following gastric bypass, pleiotrophic responses from the gastro intestinal tract may contribute to improved appetite reduction, long-term lowering of body weight, glycaemic control and improvements in end organ damage.