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

Laque A, Yu S, Qualls-Creekmore E, Gettys S, Schwartzenburg C, Bui K, Rhodes C, Berthoud HR, Morrison CD, Richards BK, Münzberg H - Mol Metab (2015)

Bottom Line: We showed earlier that LepRb neurons in the lateral hypothalamus (LHA) co-express the inhibitory acting neuropeptide galanin (GAL-LepRb neurons).LHA GAL-LepRb neurons innervate orexin neurons, but not the VTA.We suggest galanin as an important mediator of leptin action to modulate nutrient reward by inhibiting orexin neurons.

View Article: PubMed Central - PubMed

Affiliation: Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.

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-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.

No MeSH data available.


KO mice work more for sugar rewards. Incentive runway testing of WT and KO mice (n = 4 each genotype) for completion speed (cm/sec = runway length [cm]/time from leaving start box till entering goal box [sec]) (A. pANOVA < 0.05; *pHolm-Sidak < 0.05–0.01), the number of direct runs (in contrast to distracted runs) (B., C.; pANOVA < 0.05; pHolm-Sidak<*0.03, # = 0.06; pt-test < 0.03, respectively) and running speed (mean completion speed from all direct runs) (D., E.; pANOVA < 0.03; pHolm-Sidak<*0.03, ** < 0.02, # = 0.08; pt-test < 0.03, respectively). Each session consisted of 5 trials and sessions that were held every other day. WT = wildtype; KO = knock out.
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fig3: KO mice work more for sugar rewards. Incentive runway testing of WT and KO mice (n = 4 each genotype) for completion speed (cm/sec = runway length [cm]/time from leaving start box till entering goal box [sec]) (A. pANOVA < 0.05; *pHolm-Sidak < 0.05–0.01), the number of direct runs (in contrast to distracted runs) (B., C.; pANOVA < 0.05; pHolm-Sidak<*0.03, # = 0.06; pt-test < 0.03, respectively) and running speed (mean completion speed from all direct runs) (D., E.; pANOVA < 0.03; pHolm-Sidak<*0.03, ** < 0.02, # = 0.08; pt-test < 0.03, respectively). Each session consisted of 5 trials and sessions that were held every other day. WT = wildtype; KO = knock out.

Mentions: Indeed, KO mice showed an increased completion speed to obtain the sweet (fat free) treat (Figure 3A, n = 4; pANOVA < 0.05; *pHolm-Sidak < 0.05–0.01). Further analysis revealed that KO had more incidences of direct, undistracted runs, while WT mice showed significantly more runs with distractions such as pauses, falters and reversals (Figure 3B, C and videos S1, S2; n = 4; pANOVA < 0.05; pHolm-Sidak < *0.03, # = 0.06; pt-test < 0.03, respectively). In addition, KO also ran faster to obtain the treat compared to WT mice (Figure 3D, E and videos S1, S2; n = 4; pANOVA < 0.03; pHolm-Sidak < *0.03, ** < 0.02, # = 0.08; pt-test < 0.03, respectively).


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

Laque A, Yu S, Qualls-Creekmore E, Gettys S, Schwartzenburg C, Bui K, Rhodes C, Berthoud HR, Morrison CD, Richards BK, Münzberg H - Mol Metab (2015)

KO mice work more for sugar rewards. Incentive runway testing of WT and KO mice (n = 4 each genotype) for completion speed (cm/sec = runway length [cm]/time from leaving start box till entering goal box [sec]) (A. pANOVA < 0.05; *pHolm-Sidak < 0.05–0.01), the number of direct runs (in contrast to distracted runs) (B., C.; pANOVA < 0.05; pHolm-Sidak<*0.03, # = 0.06; pt-test < 0.03, respectively) and running speed (mean completion speed from all direct runs) (D., E.; pANOVA < 0.03; pHolm-Sidak<*0.03, ** < 0.02, # = 0.08; pt-test < 0.03, respectively). Each session consisted of 5 trials and sessions that were held every other day. WT = wildtype; KO = knock out.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4588437&req=5

fig3: KO mice work more for sugar rewards. Incentive runway testing of WT and KO mice (n = 4 each genotype) for completion speed (cm/sec = runway length [cm]/time from leaving start box till entering goal box [sec]) (A. pANOVA < 0.05; *pHolm-Sidak < 0.05–0.01), the number of direct runs (in contrast to distracted runs) (B., C.; pANOVA < 0.05; pHolm-Sidak<*0.03, # = 0.06; pt-test < 0.03, respectively) and running speed (mean completion speed from all direct runs) (D., E.; pANOVA < 0.03; pHolm-Sidak<*0.03, ** < 0.02, # = 0.08; pt-test < 0.03, respectively). Each session consisted of 5 trials and sessions that were held every other day. WT = wildtype; KO = knock out.
Mentions: Indeed, KO mice showed an increased completion speed to obtain the sweet (fat free) treat (Figure 3A, n = 4; pANOVA < 0.05; *pHolm-Sidak < 0.05–0.01). Further analysis revealed that KO had more incidences of direct, undistracted runs, while WT mice showed significantly more runs with distractions such as pauses, falters and reversals (Figure 3B, C and videos S1, S2; n = 4; pANOVA < 0.05; pHolm-Sidak < *0.03, # = 0.06; pt-test < 0.03, respectively). In addition, KO also ran faster to obtain the treat compared to WT mice (Figure 3D, E and videos S1, S2; n = 4; pANOVA < 0.03; pHolm-Sidak < *0.03, ** < 0.02, # = 0.08; pt-test < 0.03, respectively).

Bottom Line: We showed earlier that LepRb neurons in the lateral hypothalamus (LHA) co-express the inhibitory acting neuropeptide galanin (GAL-LepRb neurons).LHA GAL-LepRb neurons innervate orexin neurons, but not the VTA.We suggest galanin as an important mediator of leptin action to modulate nutrient reward by inhibiting orexin neurons.

View Article: PubMed Central - PubMed

Affiliation: Central Leptin Signaling Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.

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-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.

No MeSH data available.