Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence
Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence
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DOI：
10.1152/ajpregu.00174.2008
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发表时间：
2008-08-01
影响因子：
2.8
通讯作者：
Bartness, Timothy J.
中科院分区：
文献类型：
--
作者：
Song, C. Kay;Vaughan, Cheryl H.;Bartness, Timothy J.
对控制脂质动员和产热的神经回路的精确理解仍有待确定。我们一直在研究交感神经系统（SNS）的贡献白色脂肪组织（WAT）脂解主要是在西伯利亚仓鼠。中枢黑皮质素参与控制交感神经流出到WAT，此外，黑皮质素4受体（MC 4-R）似乎主要参与。我们以前发现，急性第三脑室美拉诺坦II（MTII;一种MC 3/4-R激动剂）注射增加了对肩胛间棕色脂肪组织（IBAT）的交感神经驱动（去甲肾上腺素周转）和IBAT温度。在这里，我们测试是否MC 4-R mRNA表达在IBAT SNS流出神经元使用原位杂交前者和注射的transneuronal病毒逆行道示踪剂，伪狂犬病病毒（PRV）到IBAT，后者。在整个神经轴（所有大脑部位的平均值类似于60%），包括下丘脑室旁核（PVH;类似于80%），发现了大量PRV和MC 4-R mRNA的双标记细胞。急性脑实质MTII显微注射到清醒的，自由移动的仓鼠的PVH，使用低于那些能够增加IBAT温度时，注射到第三脑室，增加IBAT温度长达4小时，作为测量的温度转发器植入组织下面。总的来说，这些数据增加了重要的支持，认为中央黑皮质素是重要的，通过控制IBAT产热SNS神经支配的组织，可能通过MC 4-Rs。
A precise understanding of neural circuits controlling lipid mobilization and thermogenesis remains to be determined. We have been studying the sympathetic nervous system (SNS) contributions to white adipose tissue (WAT) lipolysis largely in Siberian hamsters. Central melanocortins are implicated in the control of the sympathetic outflow to WAT, and, moreover, the melanocortin 4 receptors (MC4-R) appear to be principally involved. We previously found that acute third ventricular melanotan II (MTII; an MC3/4-R agonist) injections increase sympathetic drive (norepinephrine turnover) to interscapular brown adipose tissue (IBAT) and IBAT temperature. Here we tested whether MC4-R mRNA is expressed in IBAT SNS outflow neurons using in situ hybridization for the former and injections of the transneuronal viral retrograde tract tracer, pseudorabies virus (PRV) into IBAT, for the latter. Significant numbers of double-labeled cells for PRV and MC4-R mRNA were found across the neuroaxis (mean of all brain sites similar to 60%), including the hypothalamic paraventricular nucleus (PVH; similar to 80%). Acute parenchymal MTII microinjections into the PVH of awake, freely-moving hamsters, using doses below those able to increase IBAT temperature when injected into the third ventricle, increased IBAT temperature for as long as 4 h, as measured by temperature transponders implanted below the tissue. Collectively, these data add significant support to the view that central melanocortins are important in controlling IBAT thermogenesis via the SNS innervation of this tissue, likely through the MC4-Rs.