Leptin modulates nutrient reward via inhibitory galanin action on orexin neurons.
OBJECTIVE
Leptin modulates food reward via central leptin receptor (LepRb) expressing neurons. Food reward requires stimulation of midbrain dopamine neurons and is modulated by central leptin action, but the exact central mechanisms remain unclear. Stimulatory and inhibitory leptin actions on dopamine neurons have been reported, e.g. by indirect actions on orexin neurons or via direct innervation of dopamine neurons in the ventral tegmental area.


METHODS
We showed earlier that LepRb neurons in the lateral hypothalamus (LHA) co-express the inhibitory acting neuropeptide galanin (GAL-LepRb neurons). We studied the involvement of GAL-LepRb neurons to regulate nutrient reward in mice with selective LepRb deletion from galanin neurons (GAL-LepRb(KO) mice).


RESULTS
We found that the rewarding value and preference for sucrose over fat was increased in GAL-LepRb(KO) mice compared to controls. LHA GAL-LepRb neurons innervate orexin neurons, but not the VTA. Further, expression of galanin and its receptor GalR1 are decreased in the LHA of GAL-LepRb(KO) mice, resulting in increased activation of orexin neurons.


CONCLUSIONS
We suggest galanin as an important mediator of leptin action to modulate nutrient reward by inhibiting orexin neurons.
Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Amanda
A
Laque
Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Sangho
S
Yu
Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Emily
E
Qualls-Creekmore
Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Sarah
S
Gettys
Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Candice
C
Schwartzenburg
Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Kelly
K
Bui
Kovler Diabetes Center, University of Chicago, Chicago, IL, USA.
Christopher
C
Rhodes
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Hans-Rudolf
HR
Berthoud
Neurosignaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Christopher D
CD
Morrison
Genetics of Eating Behavior Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Brenda K
BK
Richards
Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.
Heike
H
Münzberg
Incentive runway; Intralipid; Lateral hypothalamus; Locus coeruleus; Sucrose; Two-bottle choice