TY - JOUR
T1 - Delineating a serotonin 1B receptor circuit for appetite suppression in mice
AU - Li, Li
AU - Wyler, Steven C.
AU - León-Mercado, Luis A.
AU - Xu, Baijie
AU - Oh, Youjin
AU - Swati,
AU - Chen, Xiameng
AU - Wan, Rong
AU - Arnold, Amanda G.
AU - Jia, Lin
AU - Wang, Guanlin
AU - Nautiyal, Katherine
AU - Hen, René
AU - Sohn, Jong Woo
AU - Liu, Chen
N1 - Publisher Copyright:
© 2022 Li et al.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - Triptans are a class of commonly prescribed antimigraine drugs. Here, we report a previously unrecognized role for them to suppress appetite in mice. In particular, frovatriptan treatment reduces food intake and body weight in diet-induced obese mice. Moreover, the anorectic effect depends on the serotonin (5-HT) 1B receptor (Htr1b). By ablating Htr1b in four different brain regions, we demonstrate that Htr1b engages in spatiotemporally segregated neural pathways to regulate postnatal growth and food intake. Moreover, Htr1b in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) contributes to the hypophagic effects of HTR1B agonists. To further study the anorexigenic Htr1b circuit, we generated Htr1b-Cre mice. We find that ARH Htr1b neurons bidirectionally regulate food intake in vivo. Furthermore, single-nucleus RNA sequencing analyses revealed that Htr1b marks a subset of AgRP neurons. Finally, we used an intersectional approach to specifically target these neurons (Htr1bAgRP neurons). We show that they regulate food intake, in part, through a Htr1bAgRP→PVH circuit.
AB - Triptans are a class of commonly prescribed antimigraine drugs. Here, we report a previously unrecognized role for them to suppress appetite in mice. In particular, frovatriptan treatment reduces food intake and body weight in diet-induced obese mice. Moreover, the anorectic effect depends on the serotonin (5-HT) 1B receptor (Htr1b). By ablating Htr1b in four different brain regions, we demonstrate that Htr1b engages in spatiotemporally segregated neural pathways to regulate postnatal growth and food intake. Moreover, Htr1b in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) contributes to the hypophagic effects of HTR1B agonists. To further study the anorexigenic Htr1b circuit, we generated Htr1b-Cre mice. We find that ARH Htr1b neurons bidirectionally regulate food intake in vivo. Furthermore, single-nucleus RNA sequencing analyses revealed that Htr1b marks a subset of AgRP neurons. Finally, we used an intersectional approach to specifically target these neurons (Htr1bAgRP neurons). We show that they regulate food intake, in part, through a Htr1bAgRP→PVH circuit.
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U2 - 10.1084/jem.20212307
DO - 10.1084/jem.20212307
M3 - Article
C2 - 35796804
AN - SCOPUS:85134360988
SN - 0022-1007
VL - 219
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
M1 - e20212307
ER -