Role of the Gastrointestinal Tract in Peptide Hormone Release and Appetite

Abstract

Far from being a passive reservoir for digestion and absorption of food, the gastrointestinal tract is a dynamic participant in the regulation of appetite and energy homeostasis. During meals, distension of the stomach and delivery of the products of carbohydrate, lipid, and protein digestion to the small intestine act synergistically to limit food intake. Satiation is induced by the activation of vagal afferent nerves terminals in gastric and intestinal walls, and the secretion of peptide hormones such as cholecystokinin, leptin, glucagon-like peptide-1, oxyntomodulin, and peptide YY from specialized mucosal cells in the stomach and small intestine. These gut peptides exert their effects by endocrine and paracrine actions, the latter via vagal afferents. The vagus interacts with the enteric nervous system and the central nervous system to coordinate satiation signaling. In addition to inhibiting appetite centers in the hypothalamus and brainstem, gut hormones prolong the exposure of the gastrointestinal tract to nutrients by slowing gastric emptying and intestinal transit. The mechanisms by which nutrients stimulate the release of gut hormones are now known to include activation of mucosal “taste” receptors and G-protein coupled receptors in the small intestine by carbohydrates, proteins, and fatty acids. Pharmacological agonists and antagonists of gut peptides are potentially useful for the management of obesity, type 2 diabetes, gastrointestinal motility disorders, and cachexia of critical illness.

Glossary

Satiety: 

The suppression of hunger in between meals that reduces the frequency of eating.

Satiation: 

The processes that terminate feeding and limit meal size i.e. the feeling of “fullness” after ingestion of food.

Orexigenic: 

Appetite-stimulating (contrasts with anorexigenic = appetite suppressing)

Enteric nervous system: 

The network of neurons in the gastrointestinal tract (collected into ­submucosal and myenteric nerve plexuses), which control gut motility, secretion, and immune function.

Migrating motor complex(es): 

Waves of activity which pass down the intestines in regular cycles during fasting, and which facilitate transport of nutrients and other substances from proximal to distal parts of the gastrointestinal tract.

Enteroendocrine cells: 

Specialized cells in the gastrointestinal tract (e.g., L cells) that secrete ­hormones such as cholecystokinin, glucagon-like peptide-1, and peptide YY in response to luminal nutrients.

Incretin: 

An endocrine transmitter produced by the gastrointestinal tract which stimulates insulin secretion in response to postprandial hyperglycemia.

Ileal brake: 

Negative feedback mechanisms, by which the transit of nutrients to the ileum stimulates vagal signaling and the release of satiating gut peptides to inhibit gastric, duodenal, and jejunal motility and secretion.

Bariatric surgery: 

Surgical therapy for obesity, to restrict gastric capacity with intestinal malabsorption (e.g., Roux-en-Y gastric bypass) or without it (e.g., laparoscopic adjustable gastric banding).

Gastroparesis: 

A clinical disorder characterized by delayed gastric emptying, in the absence of mechanical obstruction, most frequently presenting with upper gastrointestinal symptoms such as nausea and vomiting.