title: The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway.
abstract: BACKGROUND
  Motilin-induced phase III contractions have been identified as a hunger signal. These phase III contractions occur as part of the migrating motor complex (MMC), a contractility pattern of the gastrointestinal tract during fasting. The mechanism involved in this association between subjective hunger feelings and gastrointestinal motility during the MMC is largely unknown, however, as is its ability to stimulate food intake.
  
  
  OBJECTIVE
  We sought to 1) investigate the occurrence of hunger peaks and their relation to phase III contractions, 2) evaluate whether this relation was cholinergically driven, and 3) assess the ability of the motilin receptor agonist erythromycin to induce food intake.
  
  
  METHODS
  An algorithm was developed to detect hunger peaks. The association with phase III contractions was studied in 14 healthy volunteers [50% men; mean ± SEM age: 25 ± 2 y; mean ± SEM body mass index (BMI; in kg/m(2)): 23 ± 1]. The impact of pharmacologically induced phase III contractions on the occurrence of hunger peaks and the involvement of a cholinergic pathway were assessed in 14 healthy volunteers (43% men; age: 29 ± 3 y; BMI: 23 ± 1). Last, the effect of erythromycin administration on food intake was examined in 15 healthy volunteers (40% men; age: 28 ± 3 y; BMI: 22 ± 1).
  
  
  RESULTS
  The occurrence of hunger peaks and their significant association with phase III contractions was confirmed (P < 0.0001). Pharmacologically induced phase III contractions were also significantly associated with hunger peaks (P < 0.05), and this association involved a cholinergic pathway. Administering erythromycin significantly stimulated food intake compared with placebo (53% ± 13% compared with 10% ± 5%; P < 0.05).
  
  
  CONCLUSIONS
  Motilin-induced phase III contractions induced hunger feelings through a cholinergic pathway. Moreover, erythromycin stimulated food intake, suggesting a physiologic role of motilin as an orexigenic signal from the gastrointestinal tract. This trial was registered at www.clinicaltrials.gov as NCT02633579.
authors.affiliation: Translational Research Centre for Gastrointestinal Disorders (TARGID) and.
authors.forename: Eveline
authors.initials: E
authors.lastname: Deloose
authors.affiliation: Translational Research Centre for Gastrointestinal Disorders (TARGID) and.
authors.forename: Rita
authors.initials: R
authors.lastname: Vos
authors.affiliation: Translational Research Centre for Gastrointestinal Disorders (TARGID) and.
authors.forename: Pieter
authors.initials: P
authors.lastname: Janssen
authors.affiliation: Research Group on Health Psychology, Department of Psychology, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Omer
authors.initials: O
authors.lastname: Van den Bergh
authors.affiliation: Translational Research Centre for Gastrointestinal Disorders (TARGID) and.
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
authors.affiliation: Translational Research Centre for Gastrointestinal Disorders (TARGID) and.
authors.forename: Inge
authors.initials: I
authors.lastname: Depoortere
authors.affiliation: Translational Research Centre for Gastrointestinal Disorders (TARGID) and jan.tack@med.kuleuven.be.
authors.forename: Jan
authors.identifier: http://orcid.org/0000-0002-3206-6704
authors.initials: J
authors.lastname: Tack
mesh_terms: D000328:Adult; D018678:Cholinergic Agents / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D004917:Erythromycin / Q000494:pharmacology*; D005215:Fasting; D005260:Female; D005765:Gastrointestinal Agents; D006801:Humans; D006815:Hunger / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009037:Motilin / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D016065:Myoelectric Complex, Migrating / Q000187:drug effects*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D018678:Cholinergic Agents; D005765:Gastrointestinal Agents; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009037:Motilin; D004917:Erythromycin
keywords: erythromycin; food intake; hunger; migrating motor complex; motilin