INVOLVEMENT OF THE MELANOCORTIN SYSTEM IN REGUL OF LIPOLYSIS & BLOOD PRESSURE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该项目的目的是研究黑素皮质素系统参与调节脂肪分解和血压，并表征脂肪细胞中MCRs可能的替代信号通路。在小鼠3T3细胞系中分化为脂肪细胞的室内研究表明，MC5受体和可能的MC2受体参与了直接刺激脂肪分解(手稿正在准备中)，而且初步数据表明，除cAMP外，其他信号通路也参与了黑素皮质素介导的小鼠脂肪细胞的脂肪分解。下一步将对小鼠原代脂肪细胞和脂肪组织进行检查，以更好地了解MCR在白色脂肪组织中的分布和黑素皮质素系统的生物学效应。由于黑素皮质素系统在脂肪分解方面存在显著的物种差异(Boston&Cone 1996a)，因此研究其他物种脂肪组织中5种MCR的表达模式也很重要。人类)，以确定最适合研究MC4R激动剂作为减肥药开发的这些影响的物种。MC4R的一个可能的副作用是血压升高，黑素皮质素系统对血压的影响正在体内远程模型中进行研究，特别是MC3和MC4基因敲除小鼠。此外，应该确定在血压和脂肪分解方面是否存在这些潜在的物种差异。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The aim of the project is to examine the involvement of the melanocortin system in the regulation of lipolysis and blood pressure and to characterise possible alternative signalling pathways of MCRs in adipocytes. In house studies in a mouse 3T3 cell line differentiated to adipocytes indicates that the MC5 receptor and possibly also the MC2 receptor are involved in direct stimulation of lipolysis (manuscript in preparation), and furthermore preliminary data indicates that other signalling pathways than cAMP are involved in the melanocortin mediated lipolysis of mouse adipocytes. Examination of mouse primary adipocytes and fat tissue is the next step in order to obtain a better understanding of the MCR distribution and the biological effects of the melanocortin system in white adipose tissue. As significant species differences with regard to lipolysis have been described for the melanocortin system (Boston & Cone 1996a), it is also important to characterise the expression pattern of the five MCR's in fat tissue from other species (incl. humans) in order to identify the species that is most optimal for studying these effects in the development of MC4R agonists as obesity drugs. A possible side effect described for the MC4R is increased blood pressure, and the effect of the melanocortin system on blood pressure are being investigated in telemeterised in vivo models, especially MC3 and MC4 knockout mice. Furthermore, it should be established whether these potential species differences exist with regard to blood pressure as well as lipolysis.