title: Leptin does not directly affect CNS serotonin neurons to influence appetite.
abstract: Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert(cre) promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert(cre)-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function.
authors.affiliation: Department of Pharmacology, University of Cambridge, UK.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Lam
authors.forename: Gina M
authors.initials: GM
authors.lastname: Leinninger
authors.forename: Gwendolyn W
authors.initials: GW
authors.lastname: Louis
authors.forename: Alastair S
authors.initials: AS
authors.lastname: Garfield
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Marston
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Leshan
authors.forename: Erica L
authors.initials: EL
authors.lastname: Scheller
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Christensen
authors.forename: Jose
authors.initials: J
authors.lastname: Donato
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.forename: Mark L
authors.initials: ML
authors.lastname: Evans
authors.forename: Carol
authors.initials: C
authors.lastname: Elias
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Dalley
authors.forename: Denis I
authors.initials: DI
authors.lastname: Burdakov
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
authors.forename: Lora K
authors.initials: LK
authors.lastname: Heisler
mesh_terms: D000818:Animals; D001066:Appetite; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004594:Electrophysiology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007124:Immunoenzyme Techniques; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D054411:Receptors, Leptin / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin