Hindbrain Leptin Stimulation Induces Anorexia and Hyperthermia Mediated by Hindbrain Melanocortin Receptors
Hindbrain Leptin Stimulation Induces Anorexia and Hyperthermia Mediated by Hindbrain Melanocortin Receptors
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DOI：
10.1210/en.2008-1316
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发表时间：
2009-04-01
期刊：
影响因子：
4.8
通讯作者：
Grill, Harvey J.
中科院分区：
文献类型：
--
作者：
Skibicka, Karolina P.;Grill, Harvey J.
在可以介导瘦素能量平衡作用的中枢神经系统受体中，下丘脑弓状核的受体受到最大的关注。黑皮质素受体 (MC-R) 有助于下丘脑传递的瘦素的进食和能量作用。瘦素的能量平衡作用也由下丘脑外神经元介导，包括后脑孤束核。后脑瘦素受体在瘦素的食欲作用中发挥作用，但它们对其能量作用的贡献以及它们与后脑内黑皮质素系统的功能相互作用仍有待探索。在这里，对植入用于记录能量/心血管反应的遥测装置的大鼠进行了检查，以确定：1）后脑（第四心室）瘦素受体刺激是否会引发能量和心血管效应，2）这些效应会通过6周的高脂肪饮食维持而改变，3）后脑MC-Rs介导后脑瘦素输送的生热、心血管和厌食效应。结果表明，后脑瘦素受体刺激可导致核心温度和心率持久（> 6 小时）增加，并减少食物摄入量和体重。这些反应并未因高脂肪维持而改变，这与前脑瘦素输送的报道相反。用 MC-R 拮抗剂 SHU 9119 进行第四心室预处理完全消除了后脑定向瘦素引起的高热、厌食和体重减轻，但其本身没有影响。这些数据强调了后脑瘦素受体在启动能量和厌食反应中的作用，并表明 MCR 是后脑瘦素诱导的能量平衡效应下游介导的一部分，与下丘脑瘦素受体观察到的效应平行。 （内分泌学 150：1705-1711，2009）
Of the central nervous system receptors that could mediate the energy balance effects of leptin, those of the hypothalamic arcuate nucleus receive the greatest attention. Melanocortin receptors (MC-Rs) contribute to the feeding and energetic effects of hypothalamically delivered leptin. Energy balance effects of leptin are also mediated by extrahypothalamic neurons including the hindbrain nucleus tractus solitarius. Hindbrain leptin receptors play a role in leptin's anorectic effects, but their contribution to its energetic effects and their functional interaction with melanocortin systems within the hindbrain remains unexplored. Here rats implanted with telemetric devices for recording energetic/cardiovascular responses were examined to determine whether: 1) hindbrain (fourth ventricular) leptin receptor stimulation triggers energetic and cardiovascular effects, 2) these effects are altered by a 6-wk high-fat diet maintenance, and 3) hindbrain MC-Rs mediate the thermogenic, cardiovascular, and anorexic effects of hindbrain leptin delivery. Results show that hindbrain leptin receptor stimulation produced long-lasting (>6 h) increases in core temperature and heart rate and also decreased food intake and body weight. These responses were not altered by high-fat maintenance, in contrast to what has been reported for forebrain leptin delivery. Fourth ventricular pretreatment with MC-R antagonist SHU 9119 completely abolished the hyperthermia, anorexia, and body weight loss seen with hindbrain-directed leptin but had no effects of its own. These data highlight a role for hindbrain leptin receptors in the initiation of energetic and anorexic responses and show that MCRs are part of the downstream mediation of hindbrain leptin-induced energy balance effects, paralleling effects observed for hypothalamic leptin receptors. (Endocrinology 150: 1705-1711, 2009)