Leptin does not directly affect CNS serotonin neurons to influence appetite

Daniel D. Lam; Gina M. Leinninger; Gwendolyn W. Louis; Alastair S. Garfield; Oliver J. Marston; Rebecca L. Leshan; Erica L. Scheller; Lyndsay Christensen; Jose Donato; Jing Xia; Mark L. Evans; Carol Elias; Jeffrey W. Dalley; Denis I. Burdakov; Martin G. Myers; Lora K. Heisler

doi:10.1016/j.cmet.2011.03.016

Leptin does not directly affect CNS serotonin neurons to influence appetite

Daniel D. Lam, Gina M. Leinninger, Gwendolyn W. Louis, Alastair S. Garfield, Oliver J. Marston, Rebecca L. Leshan, Erica L. Scheller, Lyndsay Christensen, Jose Donato, Jing Xia, Mark L. Evans, Carol Elias, Jeffrey W. Dalley, Denis I. Burdakov, Martin G. Myers^*, Lora K. Heisler

^*Corresponding author for this work

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

64 Citations (Scopus)

Abstract

Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert(cre) promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert(cre)-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function.

Original language	English
Pages (from-to)	584-591
Number of pages	8
Journal	Cell Metabolism
Volume	13
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2011.03.016
Publication status	Published - 4 May 2011

Keywords

arcuate nucleus neurons
5-HT2C receptor
weight homeostasis
mice
brain
inhibition
activation
deletion
targets
obesity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Lam, D. D., Leinninger, G. M., Louis, G. W., Garfield, A. S., Marston, O. J., Leshan, R. L., Scheller, E. L., Christensen, L., Donato, J., Xia, J., Evans, M. L., Elias, C., Dalley, J. W., Burdakov, D. I., Myers, M. G., & Heisler, L. K. (2011). Leptin does not directly affect CNS serotonin neurons to influence appetite. Cell Metabolism, 13(5), 584-591. https://doi.org/10.1016/j.cmet.2011.03.016

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title = "Leptin does not directly affect CNS serotonin neurons to influence appetite",

abstract = "Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert(cre) promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert(cre)-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function.",

keywords = "arcuate nucleus neurons, 5-HT2C receptor, weight homeostasis, mice, brain, inhibition, activation, deletion, targets, obesity",

author = "Lam, {Daniel D.} and Leinninger, {Gina M.} and Louis, {Gwendolyn W.} and Garfield, {Alastair S.} and Marston, {Oliver J.} and Leshan, {Rebecca L.} and Scheller, {Erica L.} and Lyndsay Christensen and Jose Donato and Jing Xia and Evans, {Mark L.} and Carol Elias and Dalley, {Jeffrey W.} and Burdakov, {Denis I.} and Myers, {Martin G.} and Heisler, {Lora K.}",

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AU - Lam, Daniel D.

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AU - Marston, Oliver J.

AU - Leshan, Rebecca L.

AU - Scheller, Erica L.

AU - Christensen, Lyndsay

AU - Donato, Jose

AU - Xia, Jing

AU - Evans, Mark L.

AU - Elias, Carol

AU - Dalley, Jeffrey W.

AU - Burdakov, Denis I.

AU - Myers, Martin G.

AU - Heisler, Lora K.

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N2 - Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert(cre) promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert(cre)-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function.

AB - Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert(cre) promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert(cre)-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function.

KW - arcuate nucleus neurons

KW - 5-HT2C receptor

KW - weight homeostasis

KW - mice

KW - brain

KW - inhibition

KW - activation

KW - deletion

KW - targets

KW - obesity

U2 - 10.1016/j.cmet.2011.03.016

DO - 10.1016/j.cmet.2011.03.016

M3 - Article

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SP - 584

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JO - Cell Metabolism

JF - Cell Metabolism

IS - 5

ER -

Leptin does not directly affect CNS serotonin neurons to influence appetite

Abstract

Keywords

UN SDGs

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