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

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

67 Scopus citations

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
State	Published - May 4 2011

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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

@article{3521e9417aa144c1b75ee07a193f9598,

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 (Sertcre) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sertcre promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sertcre-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.",

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.\}",

note = "Funding Information: This work was supported by grants from the Gates Cambridge Trust (D.D.L), the Wellcome Trust WT081713 (L.K.H), the Marilyn H. Vincent Foundation and American Diabetes Association (M.G.M.), NIH (HD061539 to C.E., DK065171 to L.K.H., DK057768 and DK078056 to M.G.M.), and the Cambridge Medical Research Council Centre for Study of Obesity and Related Disorders (L.K.H., D.I.B., and M.L.E.). We thank Drs. Xiaoxi Zhuang and Streamson Chua for the gift of Sert cre and Lepr fl mice, respectively. We thank Amylin Pharmaceuticals for the generous gift of leptin. Core support was provided by NIH DK20572 and DK089503. ",

year = "2011",

month = may,

day = "4",

doi = "10.1016/j.cmet.2011.03.016",

language = "English",

volume = "13",

pages = "584--591",

journal = "Cell metabolism",

issn = "1550-4131",

number = "5",

}

TY - JOUR

T1 - Leptin does not directly affect CNS serotonin neurons to influence appetite

AU - Lam, Daniel D.

AU - Leinninger, Gina M.

AU - Louis, Gwendolyn W.

AU - Garfield, Alastair S.

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.

N1 - Funding Information: This work was supported by grants from the Gates Cambridge Trust (D.D.L), the Wellcome Trust WT081713 (L.K.H), the Marilyn H. Vincent Foundation and American Diabetes Association (M.G.M.), NIH (HD061539 to C.E., DK065171 to L.K.H., DK057768 and DK078056 to M.G.M.), and the Cambridge Medical Research Council Centre for Study of Obesity and Related Disorders (L.K.H., D.I.B., and M.L.E.). We thank Drs. Xiaoxi Zhuang and Streamson Chua for the gift of Sert cre and Lepr fl mice, respectively. We thank Amylin Pharmaceuticals for the generous gift of leptin. Core support was provided by NIH DK20572 and DK089503.

PY - 2011/5/4

Y1 - 2011/5/4

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 (Sertcre) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sertcre promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sertcre-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 (Sertcre) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sertcre promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sertcre-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.

UR - https://www.scopus.com/pages/publications/79955595479

U2 - 10.1016/j.cmet.2011.03.016

DO - 10.1016/j.cmet.2011.03.016

M3 - Article

C2 - 21531340

AN - SCOPUS:79955595479

SN - 1550-4131

VL - 13

SP - 584

EP - 591

JO - Cell metabolism

JF - Cell metabolism

IS - 5

ER -

Leptin does not directly affect CNS serotonin neurons to influence appetite

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