title: Cholecystokinin regulates satiation independently of the abdominal vagal nerve in a pig model of total subdiaphragmatic vagotomy.
abstract: The vagal nerve and gut hormones CCK and GLP-1 play important roles in the control of food intake. However, it is not clear to what extent CCK and GLP-1 increase satiation by stimulating receptors located on abdominal vagal nerve endings or via receptors located elsewhere. This study aimed to further explore the relative contribution of the abdominal vagal nerve in mediating the satiating effects of endogenous CCK and GLP-1. Total subdiaphragmatic vagotomy or sham operation was combined with administration of CCK1 and GLP-1 receptor antagonists devazepide and exendin (9-39) in 12 pigs, applying an unbalanced Latin Square within-subject design. Furthermore, effects of vagotomy on preprandial and postprandial acetaminophen absorption, glucose, insulin, GLP-1 and CCK plasma concentrations were investigated. Ad libitum liquid meal intake (mean±SEM) was similar in sham and vagotomized pigs (4180±435 and 3760±810 g/meal). Intake increased by about 20% after blockade of CCK1 receptors, independently of the abdominal vagal nerve. Food intake did not increase after blockade of GLP-1 receptors. Blockade of CCK1 and GLP-1 receptors increased circulating CCK and GLP-1 concentrations in sham pigs only, suggesting the existence of a vagal reflex mechanism in the regulation of plasma CCK1 and GLP-1 concentrations. Vagotomy decreased acetaminophen absorption and changed glucose, insulin, CCK and GLP-1 concentrations indicating a delay in gastric emptying. Our data show that at liquid feeding, satiation is decreased effectively by pharmacological blockade of CCK1 receptors. We conclude that regulation of liquid meal intake appears to be primarily regulated by CCK1 receptors not located on abdominal vagal nerve endings.
authors.affiliation: Top Institute of Food and Nutrition, Nieuwe Kanaal 9A, Wageningen, The Netherlands; The Netherlands Organization for Applied Scientific Research, TNO, Zeist, The Netherlands; Division of Human Nutrition, Wageningen University, Bomenweg 2, Wageningen, The Netherlands. Electronic address: dina.ripken@tno.nl.
authors.forename: D
authors.initials: D
authors.lastname: Ripken
authors.affiliation: Top Institute of Food and Nutrition, Nieuwe Kanaal 9A, Wageningen, The Netherlands; The Netherlands Organization for Applied Scientific Research, TNO, Zeist, The Netherlands; Division of Human Nutrition, Wageningen University, Bomenweg 2, Wageningen, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: van der Wielen
authors.affiliation: Wageningen UR Livestock Research, De Elst 1, Wageningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van der Meulen
authors.affiliation: Wageningen UR Livestock Research, De Elst 1, Wageningen, The Netherlands; Department of Animal Sciences, Animal Nutrition Group, Wageningen University, De Elst 1, Wageningen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Schuurman
authors.affiliation: Division of Human Nutrition, Wageningen University, Bomenweg 2, Wageningen, The Netherlands.
authors.forename: R F
authors.initials: RF
authors.lastname: Witkamp
authors.affiliation: Top Institute of Food and Nutrition, Nieuwe Kanaal 9A, Wageningen, The Netherlands.
authors.forename: H F J
authors.initials: HF
authors.lastname: Hendriks
authors.affiliation: Wageningen UR Livestock Research, De Elst 1, Wageningen, The Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: Koopmans
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D002766:Cholecystokinin / Q000378:metabolism*; D020109:Devazepide / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D006727:Hormone Antagonists / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D023421:Models, Animal; D010446:Peptide Fragments / Q000494:pharmacology; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism; D012527:Satiation / Q000187:drug effects / Q000502:physiology*; D034421:Sus scrofa; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology* / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D006727:Hormone Antagonists; D007328:Insulin; D010446:Peptide Fragments; D018027:Receptors, Glucagon; D000082:Acetaminophen; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; D020109:Devazepide
keywords: Cholecystokinin; Devazepide; Exendin (9–39); Food intake regulation; Glucagon-like peptide 1; Vagal nerve