Song C Kay, Jackson Raven M, Harris Ruth B S, Richard Denis, Bartness Timothy J
Department of Biology, Neurobiology and Behavior Program, Georgia State University, 24 Peachtree Center Ave NE, Atlanta, Georgia 30302-4010, USA.
Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1467-76. doi: 10.1152/ajpregu.00348.2005.
Energy balance results from the coordination of multiple pathways affecting energy expenditure and food intake. Candidate neuropeptides involved in energy balance are the melanocortins. Several species, including Siberian hamsters studied here, decrease and increase food intake in response to stimulation and blockade of the melanocortin 4-receptor (MC4-R). In addition, central application of the MC3/4-R agonist melanotan-II decreases body fat (increases lipolysis) beyond that accounted for by its ability to decrease food intake. Because an increase in the sympathetic nervous system drive to white adipose tissue (WAT) is the principal initiator of lipolysis, we tested whether the sympathetic outflow circuitry from brain to WAT contained MC4-R mRNA expressing cells. This was accomplished by labeling the sympathetic outflow to inguinal WAT using the pseudorabies virus (PRV), a transneuronal retrograde viral tract tracer, and then processing the brain for colocalization of PRV immunoreactivity with MC4-R mRNA, the latter assessed by in situ hybridization. MC4-R mRNA was impressively colocalized in PRV-labeled cells (approximately greater than 60%) in many brain areas across the neuroaxis, including those typically implicated in lipid mobilization (e.g., hypothalamic paraventricular, suprachiasmatic, arcuate and dorsomedial nuclei, lateral hypothalamic area), as well as those not traditionally identified with lipolysis (e.g., preoptic area, subzona incerta of the lateral hypothalamus, periaqueductal gray, solitary nucleus). These data provide compelling neuroanatomical evidence that could underlie a direct central modulation of the sympathetic outflow to WAT by the melanocortins through the MC4-Rs resulting in changes in lipid mobilization and adiposity.
能量平衡源于影响能量消耗和食物摄入的多种途径之间的协调。参与能量平衡的候选神经肽是黑皮质素。包括本文所研究的西伯利亚仓鼠在内的几种物种，会根据黑皮质素4受体（MC4-R）的刺激和阻断情况来减少或增加食物摄入量。此外，中枢给予MC3/4-R激动剂黑素细胞扩张素-II可减少体脂（增加脂肪分解），其作用超过了因减少食物摄入而产生的效果。由于交感神经系统对白色脂肪组织（WAT）驱动的增加是脂肪分解的主要启动因素，我们测试了从大脑到WAT的交感神经输出回路中是否含有表达MC4-R mRNA的细胞。这是通过使用伪狂犬病病毒（PRV，一种跨神经元逆行病毒示踪剂）标记到腹股沟WAT的交感神经输出，然后对大脑进行处理，以检测PRV免疫反应性与MC4-R mRNA的共定位情况来实现的，后者通过原位杂交进行评估。在整个神经轴的许多脑区中，MC4-R mRNA与PRV标记的细胞有显著的共定位（约大于60%），包括那些通常与脂质动员有关的脑区（如下丘脑室旁核、视交叉上核、弓状核和背内侧核、下丘脑外侧区），以及那些传统上未与脂肪分解相关联的脑区（如视前区、下丘脑外侧区的不确定带、导水管周围灰质、孤束核）。这些数据提供了令人信服的神经解剖学证据，表明黑皮质素可能通过MC4-R对WAT的交感神经输出进行直接的中枢调节，从而导致脂质动员和肥胖的变化。
