title: Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications.
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 CreER(T2) 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.
authors.affiliation: Department of Genetics and Development, Columbia University, New York, NY 10027, USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Yadav
authors.forename: Franck
authors.initials: F
authors.lastname: Oury
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Tiffany
authors.initials: T
authors.lastname: Thomas
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.forename: Rene
authors.initials: R
authors.lastname: Hen
authors.forename: Andree
authors.initials: A
authors.lastname: Krust
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Gerard
authors.initials: G
authors.lastname: Karsenty
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D044302:Receptor, Serotonin, 5-HT1B / Q000172:deficiency / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D020738:Leptin; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin