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Publication : Leptin modulates nutrient reward via inhibitory galanin action on orexin neurons.

First Author  Laque A Year  2015
Journal  Mol Metab Volume  4
Issue  10 Pages  706-17
PubMed ID  26500842 Mgi Jnum  J:243627
Mgi Id  MGI:5909267 Doi  10.1016/j.molmet.2015.07.002
Citation  Laque A, et al. (2015) Leptin modulates nutrient reward via inhibitory galanin action on orexin neurons. Mol Metab 4(10):706-17
abstractText  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. CONCLUSION: We suggest galanin as an important mediator of leptin action to modulate nutrient reward by inhibiting orexin neurons.
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