Cited by 412Regulation of Appetite and ObesityNeurotransmitter Receptor Influence on BehaviorHypothalamic control of reproductive hormones

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

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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, Streamson, Diano, Sabrina, Horvath, Tamas L., Seeley, Randy J., Becker, Jill B., Münzberg, Heike, Myers, Martin G.·2009·Cell Metabolism

DOI 10.1016/j.cmet.2009.06.011PMC PMC2723060

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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.

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Authors: 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.
Affiliations: University of Michigan (US)
Albert Einstein College of Medicine (US)
University of Cincinnati (US)
University of Chicago (US)
Yale University (US)
Corresponding author: Myers, Martin G.
ORCID: Leinninger, Gina M.
Jo, Young-Hwan
Yang, Hongyan
Wilson, Hilary
Opland, Darren M.
Rhodes, Christopher J.
Chua, Streamson
Diano, Sabrina
Seeley, Randy J.
Becker, Jill B.
Münzberg, Heike
Myers, Martin G.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2009-08
Volume: 10
Issue: 2
Pages: 89-98
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2009.06.011
PMC: PMC2723060
OpenAlex: W2001980298
Cited by: 412
References: 47
Citations by year: 2026: 7 · 2025: 9 · 2024: 12 · 2023: 22 · 2022: 16 · 2021: 27 · 2020: 18 · 2019: 19 · 2018: 32 · 2017: 32 · 2016: 30 · 2015: 30 · 2014: 25 · 2013: 33 · 2012: 27
FWCI: 14.97
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1446 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Diabetes Research and Training Center
American Diabetes Association
American Heart Association
National Institutes of Health
Obesity Society
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: leptin, leptin receptor, lateral hypothalamus, ventral tegmental area, mesolimbic dopamine system, feeding behavior, anorexia, inhibitory neurons, dopamine synthesis, body weight regulation, leptin deficiency
MeSH terms: Animals, Body Weight, Dopamine, Eating, Hypothalamic Area, Lateral, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Ventral Tegmental Area, Leptin, Mice, Receptors, Leptin, Gene Knock-In Techniques

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

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