Leptin Modulates Nutrient Reward Via Inhibitory Galanin Action on Orexin Neurons

Overview

Journal Mol Metab

Specialty Cell Biology

Date 2015 Oct 27

PMID 26500842

Citations 37

Authors

Amanda Laque

Sangho Yu

Emily Qualls-Creekmore

Sarah Gettys

Candice Schwartzenburg

Kelly Bui

Christopher Rhodes

Hans-Rudolf Berthoud

Christopher D Morrison

Brenda K Richards

Heike Munzberg

Affiliations

Soon will be listed here.

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.

Citing Articles

Regulation of energy balance by leptin as an adiposity signal and modulator of the reward system.

Asgari R, Caceres-Valdiviezo M, Wu S, Hamel L, Humber B, Agarwal S Mol Metab. 2024; 91():102078.

PMID: 39615837 PMC: 11696864. DOI: 10.1016/j.molmet.2024.102078.

Complementary lateral hypothalamic populations resist hunger pressure to balance nutritional and social needs.

Petzold A, van den Munkhof H, Figge-Schlensok R, Korotkova T Cell Metab. 2023; 35(3):456-471.e6.

PMID: 36827985 PMC: 10028225. DOI: 10.1016/j.cmet.2023.02.008.

Orexin neurons inhibit sleep to promote arousal.

De Luca R, Nardone S, Grace K, Venner A, Cristofolini M, Bandaru S Nat Commun. 2022; 13(1):4163.

PMID: 35851580 PMC: 9293990. DOI: 10.1038/s41467-022-31591-y.

Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals.

Garrido-Suarez B, Garrido-Valdes M, Garrido G Sleep Med. 2022; 98:79-86.

PMID: 35792321 PMC: 9212783. DOI: 10.1016/j.sleep.2022.06.011.

Lateral hypothalamic galanin neurons are activated by stress and blunt anxiety-like behavior in mice.

Owens-French J, Li S, Francois M, Townsend R, Daniel M, Soulier H Behav Brain Res. 2022; 423:113773.

PMID: 35101456 PMC: 8901126. DOI: 10.1016/j.bbr.2022.113773.

References

Adams A, Clapham J, Wynick D, Speakman J . Feeding behaviour in galanin knockout mice supports a role of galanin in fat intake and preference. J Neuroendocrinol. 2007; 20(2):199-206. DOI: 10.1111/j.1365-2826.2007.01638.x. View

Yamanaka A, Beuckmann C, Willie J, Hara J, Tsujino N, Mieda M . Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003; 38(5):701-13. DOI: 10.1016/s0896-6273(03)00331-3. View

Dong Y, Tyszkiewicz J, Fong T . Galanin and galanin-like peptide differentially modulate neuronal activities in rat arcuate nucleus neurons. J Neurophysiol. 2006; 95(5):3228-34. DOI: 10.1152/jn.01117.2005. View

Tempel D, Leibowitz K, Leibowitz S . Effects of PVN galanin on macronutrient selection. Peptides. 1988; 9(2):309-14. DOI: 10.1016/0196-9781(88)90265-3. View

Zhang Y, Kerman I, Laque A, Nguyen P, Faouzi M, Louis G . Leptin-receptor-expressing neurons in the dorsomedial hypothalamus and median preoptic area regulate sympathetic brown adipose tissue circuits. J Neurosci. 2011; 31(5):1873-84. PMC: 3069639. DOI: 10.1523/JNEUROSCI.3223-10.2011. View

Furudono Y, Ando C, Yamamoto C, Kobashi M, Yamamoto T . Involvement of specific orexigenic neuropeptides in sweetener-induced overconsumption in rats. Behav Brain Res. 2006; 175(2):241-8. DOI: 10.1016/j.bbr.2006.08.031. View

Kraft T, Yakubov Y, Huang D, Fitzgerald G, Acosta V, Natanova E . Dopamine D1 and opioid receptor antagonism effects on the acquisition and expression of fat-conditioned flavor preferences in BALB/c and SWR mice. Pharmacol Biochem Behav. 2013; 110:127-36. DOI: 10.1016/j.pbb.2013.06.009. View

Currie P, Wilson L . Potentiation of dark onset feeding in obese mice (genotype ob/ob) following central injection of norepinephrine and clonidine. Eur J Pharmacol. 1993; 232(2-3):227-34. DOI: 10.1016/0014-2999(93)90778-g. View

Faouzi M, Leshan R, Bjornholm M, Hennessey T, Jones J, Munzberg H . Differential accessibility of circulating leptin to individual hypothalamic sites. Endocrinology. 2007; 148(11):5414-23. DOI: 10.1210/en.2007-0655. View

10.

Vittoz N, Berridge C . Hypocretin/orexin selectively increases dopamine efflux within the prefrontal cortex: involvement of the ventral tegmental area. Neuropsychopharmacology. 2005; 31(2):384-95. DOI: 10.1038/sj.npp.1300807. View

11.

Smith B, Berthoud H, York D, Bray G . Differential effects of baseline macronutrient preferences on macronutrient selection after galanin, NPY, and an overnight fast. Peptides. 1997; 18(2):207-11. DOI: 10.1016/s0196-9781(96)00318-x. View

12.

Tsuda K, Tsuda S, Nishio I, Masuyama Y, Goldstein M . Effects of galanin on dopamine release in the central nervous system of normotensive and spontaneously hypertensive rats. Am J Hypertens. 1999; 11(12):1475-9. DOI: 10.1016/s0895-7061(98)00168-x. View

13.

Hawes J, Narasimhaiah R, Picciotto M . Galanin attenuates cyclic AMP regulatory element-binding protein (CREB) phosphorylation induced by chronic morphine and naloxone challenge in Cath.a cells and primary striatal cultures. J Neurochem. 2006; 96(4):1160-8. DOI: 10.1111/j.1471-4159.2005.03613.x. View

14.

Munzberg H, Huo L, Nillni E, Hollenberg A, Bjorbaek C . Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin. Endocrinology. 2003; 144(5):2121-31. DOI: 10.1210/en.2002-221037. View

15.

Carter M, De Lecea L, Adamantidis A . Functional wiring of hypocretin and LC-NE neurons: implications for arousal. Front Behav Neurosci. 2013; 7:43. PMC: 3657625. DOI: 10.3389/fnbeh.2013.00043. View

16.

Smith B, York D, Bray G . Effects of dietary preference and galanin administration in the paraventricular or amygdaloid nucleus on diet self-selection. Brain Res Bull. 1996; 39(3):149-54. DOI: 10.1016/0361-9230(95)02086-1. View

17.

Zhang M, Kelley A . Enhanced intake of high-fat food following striatal mu-opioid stimulation: microinjection mapping and fos expression. Neuroscience. 2000; 99(2):267-77. DOI: 10.1016/s0306-4522(00)00198-6. View

18.

Kyrkouli S, Stanley B, Seirafi R, Leibowitz S . Stimulation of feeding by galanin: anatomical localization and behavioral specificity of this peptide's effects in the brain. Peptides. 1990; 11(5):995-1001. DOI: 10.1016/0196-9781(90)90023-x. View

19.

McMinn J, Liu S, Dragatsis I, Dietrich P, Ludwig T, Eiden S . An allelic series for the leptin receptor gene generated by CRE and FLP recombinase. Mamm Genome. 2004; 15(9):677-85. DOI: 10.1007/s00335-004-2340-1. View

20.

Figlewicz D, Bennett J, MacDonald Naleid A, Davis C, Grimm J . Intraventricular insulin and leptin decrease sucrose self-administration in rats. Physiol Behav. 2006; 89(4):611-6. DOI: 10.1016/j.physbeh.2006.07.023. View