The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
J Exp Med. 2022 Aug 1;219(8). doi: 10.1084/jem.20212307. Epub 2022 Jul 7.
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.
曲坦类是一类常用于治疗偏头痛的药物。在这里，我们报告了它们在抑制小鼠食欲方面的一个以前未被认识的作用。具体来说，曲普坦类药物治疗可减少饮食诱导肥胖小鼠的食物摄入量和体重。此外，这种厌食作用依赖于血清素（5-HT）1B 受体（Htr1b）。通过在四个不同的脑区消除 Htr1b，我们证明 Htr1b 通过时空分离的神经通路来调节出生后生长和食物摄入。此外，Htr1b 在下丘脑弓状核（ARH）的 AgRP 神经元中对 HTR1B 激动剂的抑食作用有贡献。为了进一步研究厌食性 Htr1b 回路，我们生成了 Htr1b-Cre 小鼠。我们发现 ARH Htr1b 神经元在体内双向调节食物摄入。此外，单细胞 RNA 测序分析显示 Htr1b 标记了一组 AgRP 神经元。最后，我们使用了一种交叠的方法来特异性靶向这些神经元（Htr1bAgRP 神经元）。我们表明它们通过 Htr1bAgRP→PVH 回路调节食物摄入，部分是通过 Htr1bAgRP→PVH 回路调节食物摄入。
