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 Chua; Sabrina Diano; Tamas L. Horvath; Randy J. Seeley; Jill B. Becker; Heike Münzberg; Martin G. Myers

doi:10.1016/j.cmet.2009.06.011

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 Chua, Sabrina Diano, Tamas L. Horvath, Randy J. Seeley, Jill B. Becker, Heike Münzberg, Martin G. Myers

Medicine

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

334 Scopus citations

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 language	English (US)
Pages (from-to)	89-98
Number of pages	10
Journal	Cell metabolism
Volume	10
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2009.06.011
State	Published - Aug 6 2009

Keywords

HUMDISEASE

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

Access to Document

10.1016/j.cmet.2009.06.011

Cite this

Leinninger, G. M., Jo, Y. H., Leshan, R. L., Louis, G. W., Yang, H., Barrera, J. G., Wilson, H., Opland, D. M., Faouzi, M. A., Gong, Y., Jones, J. C., Rhodes, C. J., Chua, S., Diano, S., Horvath, T. L., Seeley, R. J., Becker, J. B., Münzberg, H., & Myers, M. G. (2009). Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding. Cell metabolism, 10(2), 89-98. https://doi.org/10.1016/j.cmet.2009.06.011

Leinninger, GM, Jo, YH, Leshan, RL, Louis, GW, Yang, H, Barrera, JG, Wilson, H, Opland, DM, Faouzi, MA, Gong, Y, Jones, JC, Rhodes, CJ, Chua, S, 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

@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 Jo, {Young Hwan} 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 Streamson Chua and Sabrina Diano and Horvath, {Tamas L.} and Seeley, {Randy J.} and Becker, {Jill B.} and Heike M{\"u}nzberg and Myers, {Martin G.}",

note = "Funding Information: We thank Amylin Pharmaceuticals for the generous gift of leptin and thank Gary Schwartz, Bob Kennedy, Maura Perry, and members of the Myers lab for helpful discussions. This work was supported by the Michigan Diabetes Research and Training Center; Michigan Comprehensive Diabetes Center; and grants from the American Diabetes Association and American Heart Association (M.G.M.), the NIH (M.G.M., C.J.R., and J.B.B.), and the Obesity Society (G.M.L.). ",

year = "2009",

month = aug,

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, Streamson

AU - Diano, Sabrina

AU - Horvath, Tamas L.

AU - Seeley, Randy J.

AU - Becker, Jill B.

AU - Münzberg, Heike

AU - Myers, Martin G.

N1 - Funding Information: We thank Amylin Pharmaceuticals for the generous gift of leptin and thank Gary Schwartz, Bob Kennedy, Maura Perry, and members of the Myers lab for helpful discussions. This work was supported by the Michigan Diabetes Research and Training Center; Michigan Comprehensive Diabetes Center; and grants from the American Diabetes Association and American Heart Association (M.G.M.), the NIH (M.G.M., C.J.R., and J.B.B.), and the Obesity Society (G.M.L.).

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

SN - 1550-4131

VL - 10

SP - 89

EP - 98

JO - Cell metabolism

JF - Cell metabolism

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this