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

研究成果: Article

58 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)41-52
ページ数12
ジャーナルJournal of Experimental Medicine
208
発行部数1
DOI
出版物ステータスPublished - 2011 1 17
外部発表Yes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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