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High-Yield Terms

  • Hypothalamus: brain region composed of several distinct nuclei, involved in coordinating the gastrointestinal and nervous systems to the endocrine system, major structure controlling appetite

  • Anorexigenic: causing appetite suppression

  • Orexigenic: causing increased appetite

  • Satiation: pertaining to the cessation of hunger

  • Satiety: the sensation of being full

  • Enteroendocrine cells: specialized endocrine cells of the gastrointestinal tract and pancreas

  • Incretin: any gut hormone associated with food intake-stimulation of insulin secretion from the pancreas

  • Oxyntic cells: parietal cells of gastric glands responsible for gastric acid secretion

  • Hypocretins: another name for the orexins

The Gut-Brain Connection

The brain, in particular the hypothalamus, plays highly critical roles in the regulation of energy metabolism, nutrient partitioning, and the control of feeding behaviors. The gastrointestinal tract is intimately connected to the actions of the hypothalamic-pituitary axis via the release of peptides that exert responses within the brain as well as through neuroendocrine and sensory inputs from the gut. The primary centers in the brain involved in the control of appetite are the hypothalamic-pituitary axis and the brain stem.

The consumption of food initiates a cascade of neuronal and hormonal responses within and by the gastrointestinal system that impact responses in the central nervous system. The brain initiates responses to feeding even before the ingestion of food. The very sight and smell of food stimulates exocrine and endocrine secretions in the gut as well as increasing gut motility. Ingestion of food stimulates mechanoreceptors leading to distension and propulsion to accommodate the food. As the food is propelled through the gut regions of the intestines secrete various hormones that circulate to the brain and impact hypothalamic responses as discussed in the sections later. The mechanoreceptor responses are transmitted via afferent nerve signals along the vagus nerve to the dorsal vagal complex in the medulla and terminating in the nucleus of the solitary tract (NTS, for the Latin term nucleus tractus solitarii). Projections from the NTS enter the visceral sensory complex of the thalamus which mediates the perception of gastrointestinal fullness and satiety. Several hormones released from the gut in response to food intake exert anorexigenic (appetite-suppressing) responses in the brain, particularly in the hypothalamus. These hormones include glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), peptide tyrosine tyrosine (PYY), pancreatic polypeptide (PP), and oxyntomodulin (OXM or OXY). A single orexigenic (appetite-stimulating) hormone, ghrelin, is known to be released by cells of the gut.

Gastrointestinal Hormones and Peptides

There are more than 30 peptides currently identified as being expressed within the digestive tract, making the gut the largest endocrine organ in the body. The regulatory peptides synthesized by the gut include hormones, peptide neurotransmitters, and growth factors. Indeed, several hormones and neurotransmitters first identified in the central nervous system and other endocrine organs have subsequently been found in endocrine cells and/or neurons of the gut (Table 44-1).

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