title: Salivary peptide tyrosine-tyrosine 3-36 modulates ingestive behavior without inducing taste aversion.
abstract: Hormone peptide tyrosine-tyrosine (PYY) is secreted into circulation from the gut L-endocrine cells in response to food intake, thus inducing satiation during interaction with its preferred receptor, Y2R. Clinical applications of systemically administered PYY for the purpose of reducing body weight were compromised as a result of the common side effect of visceral sickness. We describe here a novel approach of elevating PYY in saliva in mice, which, although reliably inducing strong anorexic responses, does not cause aversive reactions. The augmentation of salivary PYY activated forebrain areas known to mediate feeding, hunger, and satiation while minimally affecting brainstem chemoreceptor zones triggering nausea. By comparing neuronal pathways activated by systemic versus salivary PYY, we identified a metabolic circuit associated with Y2R-positive cells in the oral cavity and extending through brainstem nuclei into hypothalamic satiety centers. The discovery of this alternative circuit that regulates ingestive behavior without inducing taste aversion may open the possibility of a therapeutic application of PYY for the treatment of obesity via direct oral application.
authors.affiliation: Departments of Pediatrics and Molecular Genetics and Microbiology, College of Medicine and Department of Neuroscience and Psychiatry, Center for Smell and Taste, University of Florida, Gainesville, Florida 32610, Department of Medical Biotechnology, Udmurt State University, 426034 Izhevsk, Russia, and Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Hurtado
authors.forename: Valeriy G
authors.initials: VG
authors.lastname: Sergeyev
authors.forename: Andres
authors.initials: A
authors.lastname: Acosta
authors.forename: Michael
authors.initials: M
authors.lastname: Spegele
authors.forename: Michael
authors.initials: M
authors.lastname: La Sala
authors.forename: Nickolas J
authors.initials: NJ
authors.lastname: Waler
authors.forename: Juan
authors.initials: J
authors.lastname: Chiriboga-Hurtado
authors.forename: Seth W
authors.initials: SW
authors.lastname: Currlin
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Cedrick D
authors.initials: CD
authors.lastname: Dotson
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Gorbatyuk
authors.forename: Sergei
authors.initials: S
authors.lastname: Zolotukhin
mesh_terms: D000628:Aminophylline; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010121:Oxytocin / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D019894:Peptide YY / Q000737:chemistry / Q000172:deficiency*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012463:Saliva / Q000201:enzymology*; D012527:Satiation / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D007456:Iodine Isotopes; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D019894:Peptide YY; D014667:Vasopressins; D000628:Aminophylline; D010121:Oxytocin; D000521:alpha-MSH; D052216:Glucagon-Like Peptide 1; D014446:Tyrosine 3-Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases