title: Serotonin reciprocally regulates melanocortin neurons to modulate food intake.
abstract: The neural pathways through which central serotonergic systems regulate food intake and body weight remain to be fully elucidated. We report that serotonin, via action at serotonin1B receptors (5-HT1BRs), modulates the endogenous release of both agonists and antagonists of the melanocortin receptors, which are a core component of the central circuitry controlling body weight homeostasis. We also show that serotonin-induced hypophagia requires downstream activation of melanocortin 4, but not melanocortin 3, receptors. These results identify a primary mechanism underlying the serotonergic regulation of energy balance and provide an example of a centrally derived signal that reciprocally regulates melanocortin receptor agonists and antagonists in a similar manner to peripheral adiposity signals.
authors.affiliation: Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 2QQ, United Kingdom. lkh30@medschl.cam.ac.uk
authors.forename: Lora K
authors.initials: LK
authors.lastname: Heisler
authors.forename: Erin E
authors.initials: EE
authors.lastname: Jobst
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sutton
authors.forename: Ligang
authors.initials: L
authors.lastname: Zhou
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Borok
authors.forename: Zoe
authors.initials: Z
authors.lastname: Thornton-Jones
authors.forename: Hong Yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Zigman
authors.forename: Nina
authors.initials: N
authors.lastname: Balthasar
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kishi
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Lee
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Aschkenasi
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Olivier
authors.initials: O
authors.lastname: Boss
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Mountjoy
authors.forename: Peter G
authors.initials: PG
authors.lastname: Clifton
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Friedman
authors.forename: Tamas
authors.initials: T
authors.lastname: Horvath
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Butler
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cowley
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D044104:Receptor, Melanocortin, Type 3 / Q000502:physiology*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D044101:Receptors, Melanocortin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists
chemical_list: C097067:CP 94253; C470053:Mc3r protein, mouse; D011725:Pyridines; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D044302:Receptor, Serotonin, 5-HT1B; D044101:Receptors, Melanocortin; D058825:Serotonin 5-HT1 Receptor Agonists; D012701:Serotonin