TY - JOUR
T1 - Leptin-dependent serotonin control of appetite
T2 - Temporal specificity, transcriptional regulation, and therapeutic implications
AU - Yadav, Vijay K.
AU - Oury, Franck
AU - Tanaka, Kenji
AU - Thomas, Tiffany
AU - Wang, Ying
AU - Cremers, Serge
AU - Hen, Rene
AU - Krust, Andree
AU - Chambon, Pierre
AU - Karsenty, Gerard
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/1/17
Y1 - 2011/1/17
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20101940
DO - 10.1084/jem.20101940
M3 - Article
C2 - 21187319
AN - SCOPUS:78651495664
VL - 208
SP - 41
EP - 52
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 1
ER -