COBRE in Mesenchymal and Neural Regulation of Metabolic Networks - Metabolic Phenotyping Equipment

COBRE 在代谢网络的间充质和神经调节中的作用 - 代谢表型设备

• 批准号: 10396172
• 负责人: Lucy Liaw
• 金额: $ 24.9万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396172
• 关键词: Address; Adipocytes; Adipose tissue; Administrative Supplement; Aging; Behavior monitoring; Behavioral; Biochemical Pathway; Bioenergetics; Bone Marrow; Bone Tissue; Brown Fat; Centers of Research Excellence; Chronic Disease; Controlled Study; Core Facility; Development; Disease; Enhancement Technology; Equipment; Fracture; Funding; Genetic; Goals; Health; Histopathology; Human; Martes zibellina; Mesenchymal; Metabolic; Metabolism; Molecular; Neuraxis; Nutritional; Obesity; Osteoporosis; Physiology; Pilot Projects; Play; Process; Productivity; Proteomics; Regulation; Research; Research Personnel; Risperidone; Role; Signal Pathway; Signal Transduction; Skeleton; Stress; Sympathetic Nervous System; System; Temperature; Testing; Tissues; United States National Institutes of Health; atypical antipsychotic; behavioral phenotyping; bone loss; brain tissue; fracture risk; induced pluripotent stem cell; lipid biosynthesis; lipidomics; metabolic phenotype; mouse model; neuroregulation; novel; osteoblast differentiation; osteoprogenitor cell; precursor cell; programs; recruit; skeletal; treadmill

Abstract Whole body metabolism is regulated by integration of multiple tissues, including adipose tissue, the skeleton, and bone marrow. Imbalanced regulation of these tissues leads to prevalent, chronic disorders, obesity and osteoporosis. Adipocyte precursors and osteoprogenitor cells share a common mesenchymal precursor, and are highly regulated during aging, under nutritional stress, and in temperature regulation. There is growing appreciation that the sympathetic nervous system plays a unique role in metabolic regulation in normal health and disease, although mechanisms are just starting to be uncovered. Our program goal is to define specific molecular and signaling pathways that integrate brain, bone, and adipose tissue regulation of metabolic networks. This COBRE was initiated with four projects that test complementary aspects of adipocyte and skeletal metabolic function, and their regulation by central nervous system input. Project 1 (A. Brown) studies the role of BMP signaling in brown adipogenesis and thermogenic activity, and is optimizing thermogenic capacity in human iPS-derived brown adipocytes. Project 2 (M. Reagan) addressed bone marrow adipose tissue, a depot that is regulated during osteoporosis and obesity. Dr. Reagan has graduated with her own independent R37 funding. Her project was replaced by A. Guntur, who studies mechanisms of mitophagy and cellular bioenergetics in osteoblast differentiation. Project 3 (C. Duarte) is a translational project addressing the consequences of atypical antipsychotics on bone fracture risk. Project 4 (K. Motyl) is complementary to Project 3, and uses mouse models to test the novel hypothesis that risperidone acts on the central nervous system to target bone loss directly or via activation of brown adipose tissue. Dr. Motyl will be graduating this year, as she will be receiving her first R01. Two new junior investigator recruits are in process, and COBRE unobligated funds have been set aside for these recruitments. The COBRE projects are supported by an Administrative and Professional Development Core that oversees a pilot project program. Our successful pilot project program has supported investigators who have gone on to acquire NIH funding. We also support the scientific cores: (i) Proteomics and Lipidomics Core (C. Vary), (ii) Histopathology and Histomorphometry Core (V. Lindner), and (iii) Physiology Core (C. Rosen). This administrative supplement request is for a Promethion 8 cage multiplexed metabolic and behavioral monitoring system with temperature cabinet from Sable Systems, which will enhance our current 16 cage system and address the high demand, which is causing a bottleneck in research productivity. In addition, this acquisition will allow for the implementation of a treadmill and temperature controlled studies as part of the metabolic and behavioral capacity of this core facility.

摘要 全身新陈代谢由多种组织的整合来调节，包括脂肪组织、骨骼、 和骨髓。这些组织的不平衡调节会导致流行的慢性疾病、肥胖和 骨质疏松。脂肪细胞前体和骨祖细胞共享共同的间充质前体，并且 在衰老、营养压力和温度调节中受到高度调控。有越来越多的 了解交感神经系统在正常健康的代谢调节中起着独特的作用 和疾病，尽管机制才刚刚开始被发现。我们的计划目标是定义具体的 整合脑、骨和脂肪组织调节代谢的分子和信号通路 网络。这个Cobre项目是由四个项目发起的，这些项目测试脂肪细胞和 骨骼代谢功能，以及中枢神经系统输入对它们的调节。项目1(A.Brown)研究 BMP信号在棕色脂肪生成和生热活性中的作用，并正在优化生热 人诱导性多能干细胞来源的棕色脂肪细胞的能力。项目2(M.Reagan)解决了骨髓脂肪 组织，在骨质疏松症和肥胖期间受到调节的储存库。里根博士毕业于她自己的大学 独立的R37基金。她的项目由A·冈图尔取代，他研究有丝分裂的机制和 成骨细胞分化中的细胞生物能量学。项目3(C.Duarte)是一个翻译项目 非典型抗精神病药物对骨折风险的影响。项目4(K.Motyl)是对 项目3，并使用小鼠模型来检验利培酮作用于中枢神经系统的新假说 直接或通过激活棕色脂肪组织靶向骨丢失的系统。莫特尔博士将在毕业典礼上 今年，因为她将收到她的第一个R01。两名新的初级调查员正在招聘中，科布雷 已经为这些招聘留出了未承付的资金。科布雷项目得到了一个 监督试点项目计划的行政和专业发展核心。我们成功的试行 项目计划支持了那些继续获得NIH资金的调查人员。我们也支持 科学核心：(一)蛋白质组学和脂质组学核心(C.Varie)，(二)组织病理学和组织形态计量学 核心(V.Lindner)和(Iii)生理学核心(C.Rosen)。此行政补充申请是针对 带温度柜的甲氧磷8笼多路代谢行为监测系统 来自Sable Systems，这将增强我们目前的16笼系统，并满足高需求，即 造成了研究生产率的瓶颈。此外，此次收购将允许实施 跑步机和温度控制研究作为核心代谢和行为能力的一部分 设施。