Leptin modulates nutrient reward via inhibitory galanin action on orexin neurons

Abstract 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...

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Published in:Molecular metabolism (Germany) 2015-10, Vol.4 (10), p.706-717
Main Authors: Laque, Amanda, Yu, Sangho, Qualls-Creekmore, Emily, Gettys, Sarah, Schwartzenburg, Candice, Bui, Kelly, Rhodes, Christopher, Berthoud, Hans-Rudolf, Morrison, Christopher D, Richards, Brenda K, Münzberg, Heike
Format: Article
Language:English
Subjects:
Endocrinology & Metabolism
Incentive runway
Intralipid
Lateral hypothalamus
Locus coeruleus
Original
Sucrose
Two-bottle choice
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Summary:Abstract 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-LepRbKO mice). Results We found that the rewarding value and preference for sucrose over fat was increased in GAL-LepRbKO 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-LepRbKO mice, resulting in increased activation of orexin neurons. Conclusion We suggest galanin as an important mediator of leptin action to modulate nutrient reward by inhibiting orexin neurons.
ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2015.07.002