Serotonin reciprocally regulates melanocortin neurons to modulate food intake.
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.
Heisler
Lora K
LK
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 2QQ, United Kingdom. lkh30@medschl.cam.ac.uk
Jobst
Erin E
EE
Sutton
Gregory M
GM
Zhou
Ligang
L
Borok
Erzsebet
E
Thornton-Jones
Zoe
Z
Liu
Hong Yan
HY
Zigman
Jeffrey M
JM
Balthasar
Nina
N
Kishi
Toshiro
T
Lee
Charlotte E
CE
Aschkenasi
Carl J
CJ
Zhang
Chen-Yu
CY
Yu
Jia
J
Boss
Olivier
O
Mountjoy
Kathleen G
KG
Clifton
Peter G
PG
Lowell
Bradford B
BB
Friedman
Jeffrey M
JM
Horvath
Tamas
T
Butler
Andrew A
AA
Elmquist
Joel K
JK
Cowley
Michael A
MA
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
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