Leptin-dependent serotonin control of appetite: Temporal specificity, transcriptional regulation, and therapeutic implications

Vijay K. Yadav, Franck Oury, Kenji Tanaka, Tiffany Thomas, Ying Wang, Serge Cremers, Rene Hen, Andree Krust, Pierre Chambon, Gerard Karsenty

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Recent evidence indicates that leptin regulates appetite and energy expenditure, at least in part by inhibiting serotonin synthesis and release from brainstem neurons. To demonstrate that this pathway works postnatally, we used a conditional, brainstem-specific mouse CreERT2 driver to show that leptin signals in brainstem neurons after birth to decrease appetite by inhibiting serotonin synthesis. Cell-specific gene deletion experiments and intracerebroventricular leptin infusions reveal that serotonin signals in arcuate nuclei of the hypothalamus through the Htr1a receptor to favor food intake and that this serotonin function requires the expression of Creb, which regulates the expression of several genes affecting appetite. Accordingly, a specific antagonist of the Htr1a receptor decreases food intake in leptin-deficient but not in Htr1a-/- mice. Collectively, these results establish that leptin inhibition of serotonin is necessary to inhibit appetite postnatally and provide a proof of principle that selective inhibition of this pathway may be a viable option to treat appetite disorders.

Original languageEnglish
Pages (from-to)41-52
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number1
DOIs
Publication statusPublished - 2011 Jan 17

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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