Gastrointestinal hormones regulating appetite

Abstract

The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance. Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation. Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood–brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the central nervous system. In this way, hormonal signals from the gut may be translated into the subjective sensation of satiety. Moreover, the importance of the brain–gut axis in the control of food intake is reflected in the dual role exhibited by many gut peptides as both hormones and neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons projecting both into and out of areas of the central nervous system critical to energy balance. The global increase in the incidence of obesity and the associated burden of morbidity has imparted greater urgency to understanding the processes of appetite control. Appetite regulation offers an integrated model of a brain–gut axis comprising both endocrine and neurological systems. As physiological mediators of satiety, gut hormones offer an attractive therapeutic target in the treatment of obesity.