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

黑皮质素系统参与脂肪分解的调节

• 批准号: 8357858
• 负责人: KEVIN L GROVE
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357858
• 关键词: 3T3 Cells; Adipocytes; Adipose tissue; Adverse effects; Agonist; Biological; Blood Pressure; Boston; Cell Line; Cyclic AMP; Data; Development; Fatty acid glycerol esters; Funding; Grant; Housing; Human; Knockout Mice; Lipolysis; Manuscripts; Mediating; Melanocortin 2 Receptor; Mus; National Center for Research Resources; Obesity; Pattern; Pharmaceutical Preparations; Preparation; Primates; Principal Investigator; Regulation; Research; Research Infrastructure; Resources; Retinal Cone; Signal Pathway; Source; System; Tissues; United States National Institutes of Health; cost; in vivo Model; receptor; species difference

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该项目的目的是检查黑皮质素系统在脂肪分解和血压调节中的参与，并表征脂肪细胞中 MCR 可能的替代信号通路。对分化为脂肪细胞的小鼠 3T3 细胞系进行的内部研究表明，MC5 受体以及可能还有 MC2 受体参与了脂肪分解的直接刺激（手稿正在准备中），而且初步数据表明除 cAMP 之外的其他信号通路也参与了黑皮质素介导的小鼠脂肪细胞的脂肪分解。下一步是对小鼠原代脂肪细胞和脂肪组织进行检查，以便更好地了解白色脂肪组织中 MCR 的分布和黑皮质素系统的生物效应。由于黑皮质素系统在脂肪分解方面存在显着的物种差异（Boston & Cone 1996a），因此表征其他物种（包括人类）脂肪组织中五种 MCR 的表达模式也很重要，以便确定最适合研究 MC4R 激动剂作为肥胖药物开发中这些效应的物种。 MC4R 的一个可能的副作用是血压升高，并且正在遥测体内模型中研究黑皮质素系统对血压的影响，特别是 MC3 和 MC4 敲除小鼠。此外，应该确定这些潜在的物种差异在血压和脂肪分解方面是否存在。