Appetite signaling: from gut peptides and enteric nerves to brain.
The signaling systems underlying eating behavior control are complex. The current review focuses on gastrointestinal (GI) signaling systems as physiological key functions for metabolic control. Many of the peptides that are involved in the regulation of food intake in the brain are also found in the enteric nervous system and enteroendocrine cells of the mucosa of the GI tract. The only identified hunger-driving signal from the GI tract is ghrelin, which is mainly found in the mucosa of the stomach. Neuropeptides in the brain that influence food intake, of which neuropeptide Y, agouti gene-related peptide and orexins are stimulatory, while melanocortins and alpha-melanocortin stimulating hormone are inhibitory, are influenced by peptide signaling from the gut. These effects may take place directly through action of gut peptide in the brain or through nervous signaling from the periphery to the brain. The criteria for considering a gut hormone or neurotransmitter in a satiety signal seem to be fulfilled for cholecystokinin, glucagon-like peptide-1 and peptide YY(3-36). Other endogenous gut signals do not fulfill these criteria as they do not increase food intake in knock-out animals or in response to receptor antagonism, or display an inconsistent temporal profile with satiety and termination of the meal. Satiety signals from the GI tract act through the arcuate nucleus of the hypothalamus and the solitary tract nucleus of the brain stem, where neuronal networks directly linked to hypothalamic centers for food intake and eating behavior are activated. We have primarily focused on GI effects of various gut peptides involved in the regulation of food intake, using motor activity as a biomarker for the understanding of gut peptide effects promoting satiety.
Näslund
Erik
E
Karolinska Institutet, Division of Surgery, Danderyd Hospital, and Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden.
Hellström
Per M
PM
D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D017615:Enteric Nervous System / Q000502:physiology*; D005768:Gastrointestinal Hormones / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000294:innervation / Q000502:physiology; D006801:Humans; D009765:Obesity / Q000503:physiopathology; D012527:Satiation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D005768:Gastrointestinal Hormones