Leptin does not directly affect CNS serotonin neurons to influence appetite

Daniel D. Lam, Gina M. Leinninger, Gwendolyn W. Louis, Alastair S. Garfield, Oliver J. Marston, Rebecca L. Leshan, Erica L. Scheller, Lyndsay Christensen, Jose Donato, Jing Xia, Mark L. Evans, Carol Elias, Jeffrey W. Dalley, Denis I. Burdakov, Martin G. Myers*, Lora K. Heisler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)


Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert(cre) promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert(cre)-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function.

Original languageEnglish
Pages (from-to)584-591
Number of pages8
JournalCell Metabolism
Issue number5
Publication statusPublished - 4 May 2011


  • arcuate nucleus neurons
  • 5-HT2C receptor
  • weight homeostasis
  • mice
  • brain
  • inhibition
  • activation
  • deletion
  • targets
  • obesity


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