Department of Pharmacology, University of Cambridge, UK.
Cell Metab. 2011 May 4;13(5):584-91. doi: 10.1016/j.cmet.2011.03.016.
Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert(cre) promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert(cre)-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function.
血清素（5-HT）和瘦素在能量平衡的调节中发挥重要作用。在这里，我们研究了瘦素可能与中枢神经系统 5-HT 途径相互作用影响食欲的机制。尽管一些瘦素受体（LepRb）神经元位于背侧中缝（DR）的 5-HT 神经元附近，但 5-HT 神经元不表达 LepRb。事实上，虽然瘦素使一些非 5-HT DR 神经元超极化，但瘦素不会改变 DR 5-HT 神经元的活性。此外，5-HT 耗竭不会损害瘦素的厌食作用。血清素转运体-cre 等位基因（Sert(cre)）在 5-HT（和发育中的一些非 5-HT）神经元中表达。虽然 Sert(cre)在下丘脑的少数 LepRb 神经元中促进 LepRb 缺失，但它在 DR LepRb 神经元中不活跃，并且在小鼠中神经元特异性 Sert(cre)介导的 LepRb 失活不会改变体重或肥胖。因此，瘦素不会直接影响 5-HT 神经元，也不会通过 5-HT 神经元功能显著调节重要的食欲相关决定因素。
