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Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding
Open accessAbstract
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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“But clearly, leptin receptors are located in other hypothalamic areas such as the ventromedial, dorsomedial, and premammillary nuclei, as well as the lateral and perifornical areas where they likely contribute to leptin's effects on food intake and energy expenditure”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [101]
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“Recent investigations show that lateral hypothalamic neurons expressing orexin ([77](#B77), [199](#B199)) and other transmitters such as neurotensin ([101](#B101), [107](#B107)) provide modulatory input to midbrain dopamine neurons”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [101]
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Metadata
- 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
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 10
- Issue
- 2
- Pages
- 89-98
- ISSN
- 1550-4131 (ISSN-L)
- 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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