title: Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action.
abstract: Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions. LepRb neurons are found throughout the brain, and several distinct populations contribute to energy homeostasis control. However, the function of most LepRb populations remains unknown, and their contribution to regulate energy homeostasis has not been studied. Galanin has been hypothesized to interact with the leptin signaling system, but literature investigating colocalization of LepRb and galanin has been inconsistent, which is likely due to technical difficulties to visualize both. We used reporter mice with green fluorescent protein expression from the galanin locus to recapitulate the colocalization of galanin and leptin-induced p-STAT3 as a marker for LepRb expression. Here, we report the existence of two populations of galanin-expressing LepRb neurons (Gal-LepRb neurons): in the hypothalamus overspanning the perifornical area and adjacent dorsomedial and lateral hypothalamus [collectively named extended perifornical area (exPFA)] and in the brainstem (nucleus of the solitary tract). Surprisingly, despite the known orexigenic galanin action, leptin induces galanin mRNA expression and stimulates LepRb neurons in the exPFA, thus conflicting with the expected anorexigenic leptin action. However, we confirmed that intra-exPFA leptin injections were indeed sufficient to mediate anorexic responses. Interestingly, LepRb and galanin-expressing neurons are distinct from orexin or melanin-concentrating hormone (MCH)-expressing neurons, but exPFA galanin neurons colocalized with the anorexigenic neuropeptides neurotensin and cocaine- and amphetamine-regulated transcript (CART). Based on galanin's known inhibitory function, we speculate that in exPFA Gal-LepRb neurons galanin acts inhibitory rather than orexigenic.
authors.affiliation: Department of Central Leptin Signaling, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Laque
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sarah
authors.initials: S
authors.lastname: Gettys
authors.forename: Tu-Anh
authors.initials: TA
authors.lastname: Nguyen
authors.forename: Kelly
authors.initials: K
authors.lastname: Bui
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Morrison
authors.forename: Heike
authors.initials: H
authors.lastname: Münzberg
mesh_terms: D000818:Animals; D002452:Cell Count; D003078:Colchicine / Q000494:pharmacology; D004435:Eating / Q000235:genetics / Q000502:physiology*; D019004:Galanin / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology* / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology; D011401:Promoter Regions, Genetic; D054411:Receptors, Leptin / Q000235:genetics / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D020738:Leptin; D009479:Neuropeptides; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D049452:Green Fluorescent Proteins; D019004:Galanin; D003078:Colchicine
keywords: food intake; lateral hypothalamus; neuropeptides; nucleus of the solitary tract; perifornical area