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

Research output: Contribution to journalArticle

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

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    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