Rowett Institute, University of Aberdeen, Aberdeen, UK; Department of Pharmacology, University of Cambridge, Cambridge, UK.
Rowett Institute, University of Aberdeen, Aberdeen, UK.
Cell Metab. 2018 Oct 2;28(4):619-630.e5. doi: 10.1016/j.cmet.2018.07.017. Epub 2018 Aug 23.
To meet the challenge to human health posed by obesity, a better understanding of the regulation of feeding is essential. Medications targeting 5-hydroxytryptamine (5-HT; serotonin) 2C receptors (htr2c; 5-HTR) improve obesity. Here we probed the functional significance of 5-HTRs specifically within the brainstem nucleus of the solitary tract (5-HTR) in feeding behavior. Selective activation of 5-HTR decreased feeding and was sufficient to mediate acute food intake reductions elicited by the 5-HTR agonist obesity medication lorcaserin. Similar to pro-opiomelanocortin neurons expressed within the hypothalamic arcuate nucleus (POMC), a subset of POMC neurons co-expressed 5-HTRs and were activated by 5-HTR agonists. Knockdown of POMC prevented the acute appetite-suppressive effect of lorcaserin, whereas POMC knockdown prevented the full anorectic effect. These data identify 5-HTR as a sufficient subpopulation of 5-HTRs in reducing food intake when activated and reveal that 5-HTR agonist obesity medications require POMC within the NTS and ARC to reduce food intake.
为了应对肥胖给人类健康带来的挑战，深入了解进食的调节机制至关重要。靶向 5-羟色胺（5-HT；血清素）2C 受体（htr2c；5-HTR）的药物可改善肥胖症。在这里，我们探究了脑干孤束核（5-HTR）内 5-HTR 对进食行为的功能意义。选择性激活 5-HTR 可减少进食，足以介导 5-HTR 激动剂肥胖药物lorcaserin 引起的急性食物摄入量减少。类似于在下丘脑弓状核（POMC）内表达的前阿黑皮素原神经元（POMC），POMC 神经元的一部分共表达 5-HTR 并被 5-HTR 激动剂激活。POMC 的敲低可阻止 lorcaserin 的急性食欲抑制作用，而 POMC 的敲低则可阻止完全的厌食作用。这些数据表明，当被激活时，5-HTR 是减少食物摄入的充分的 5-HTR 亚群，并揭示了 5-HTR 激动剂肥胖药物需要 NTS 和 ARC 中的 POMC 来减少食物摄入。
