Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding

Gina M. Leinninger, Young-Hwan Jo, Rebecca L. Leshan, Gwendolyn W. Louis, Hongyan Yang, Jason G. Barrera, Hilary Wilson, Darren M. Opland, Miro A. Faouzi, Yusong Gong, Justin C. Jones, Christopher J. Rhodes, Streamson C. Chua, Jr., Sabrina Diano, Tamas L. Horvath, Randy J. Seeley, Jill B. Becker, Heike Münzberg, Martin G. Myers

Research output: Contribution to journalArticle

252 Citations (Scopus)

Abstract

The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalCell Metabolism
Volume10
Issue number2
DOIs
StatePublished - Aug 6 2009

Fingerprint

Leptin Receptors
Lateral Hypothalamic Area
Leptin
Dopamine
Neurons
Ventral Tegmental Area
Motivation
Body Weight
Hormones
Enzymes
Population

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding. / Leinninger, Gina M.; Jo, Young-Hwan; Leshan, Rebecca L.; Louis, Gwendolyn W.; Yang, Hongyan; Barrera, Jason G.; Wilson, Hilary; Opland, Darren M.; Faouzi, Miro A.; Gong, Yusong; Jones, Justin C.; Rhodes, Christopher J.; Chua, Jr., Streamson C.; Diano, Sabrina; Horvath, Tamas L.; Seeley, Randy J.; Becker, Jill B.; Münzberg, Heike; Myers, Martin G.

In: Cell Metabolism, Vol. 10, No. 2, 06.08.2009, p. 89-98.

Research output: Contribution to journalArticle

Leinninger, GM, Jo, Y-H, Leshan, RL, Louis, GW, Yang, H, Barrera, JG, Wilson, H, Opland, DM, Faouzi, MA, Gong, Y, Jones, JC, Rhodes, CJ, Chua, Jr., SC, Diano, S, Horvath, TL, Seeley, RJ, Becker, JB, Münzberg, H & Myers, MG 2009, 'Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding', Cell Metabolism, vol. 10, no. 2, pp. 89-98. https://doi.org/10.1016/j.cmet.2009.06.011
Leinninger, Gina M. ; Jo, Young-Hwan ; Leshan, Rebecca L. ; Louis, Gwendolyn W. ; Yang, Hongyan ; Barrera, Jason G. ; Wilson, Hilary ; Opland, Darren M. ; Faouzi, Miro A. ; Gong, Yusong ; Jones, Justin C. ; Rhodes, Christopher J. ; Chua, Jr., Streamson C. ; Diano, Sabrina ; Horvath, Tamas L. ; Seeley, Randy J. ; Becker, Jill B. ; Münzberg, Heike ; Myers, Martin G. / Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding. In: Cell Metabolism. 2009 ; Vol. 10, No. 2. pp. 89-98.
@article{702623bd273b4e4ea09e9bde3842ee2e,
title = "Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding",
abstract = "The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.",
keywords = "HUMDISEASE",
author = "Leinninger, {Gina M.} and Young-Hwan Jo and Leshan, {Rebecca L.} and Louis, {Gwendolyn W.} and Hongyan Yang and Barrera, {Jason G.} and Hilary Wilson and Opland, {Darren M.} and Faouzi, {Miro A.} and Yusong Gong and Jones, {Justin C.} and Rhodes, {Christopher J.} and {Chua, Jr.}, {Streamson C.} and Sabrina Diano and Horvath, {Tamas L.} and Seeley, {Randy J.} and Becker, {Jill B.} and Heike M{\"u}nzberg and Myers, {Martin G.}",
year = "2009",
month = "8",
day = "6",
doi = "10.1016/j.cmet.2009.06.011",
language = "English (US)",
volume = "10",
pages = "89--98",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding

AU - Leinninger, Gina M.

AU - Jo, Young-Hwan

AU - Leshan, Rebecca L.

AU - Louis, Gwendolyn W.

AU - Yang, Hongyan

AU - Barrera, Jason G.

AU - Wilson, Hilary

AU - Opland, Darren M.

AU - Faouzi, Miro A.

AU - Gong, Yusong

AU - Jones, Justin C.

AU - Rhodes, Christopher J.

AU - Chua, Jr., Streamson C.

AU - Diano, Sabrina

AU - Horvath, Tamas L.

AU - Seeley, Randy J.

AU - Becker, Jill B.

AU - Münzberg, Heike

AU - Myers, Martin G.

PY - 2009/8/6

Y1 - 2009/8/6

N2 - The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.

AB - The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these LHA LepRb neurons innervate the VTA, and leptin action on these neurons restores VTA expression of the rate-limiting enzyme in DA production along with mesolimbic DA content in leptin-deficient animals. Thus, these findings reveal that LHA LepRb neurons link anorexic leptin action to the mesolimbic DA system.

KW - HUMDISEASE

UR - http://www.scopus.com/inward/record.url?scp=67849092898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67849092898&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2009.06.011

DO - 10.1016/j.cmet.2009.06.011

M3 - Article

C2 - 19656487

AN - SCOPUS:67849092898

VL - 10

SP - 89

EP - 98

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 2

ER -