Functional characterization of brown adipose tissue in phylogenetically ancient eutherian mammals, Afrotheria

系统发育上古老的真兽类哺乳动物非洲兽亚目棕色脂肪组织的功能特征

• 批准号: 157015876
• 负责人: Professor Dr. Gerhard Heldmaier
• 金额: --
• 依托单位: Fachbereich 17: Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/157015876?language=en
• 关键词: Functional; characterization; brown; adipose; tissue

This study aims to further investigate the role of brown adipose tissue (BAT), the function of its thermogenic protein uncoupling protein-1 (UCP1) and the plasticity of adaptive non-shivering thermogenesis in the evolutionary most basal group of the eutherian mammals, the Afrotheria (Elephantulus. myurus, Elephantulus edwardii, Amblysomus hottentottus longiceps, Echinops telfairi). The central goal of our proposed project is to reveal whether or not Afrotherian thermogenic brown adipose already conveys all currently known key features necessary to infer classical non-shivering thermogenesis. Our approach is scaling from in vivo metabolic responses (torpor behaviour, capacity for nonshivering heat production) in free ranging animals, during different seasons, to the molecular mechanism of heat production. Molecular parameters and bioenergetics in isolated BAT mitochondria of E. edwardii and E. telfairi will be investigated with respect to sophisticated technologies accessing thermogenic proteins by mitochondrial proton leak kinetics in vitro and in vivo. For the latter, UCP1 cDNAs from E. myurus, E. edwardii, A. h. longiceps, and E. telfairi will be cloned and stably transfected into in HEK293 (human embryonic kidney) cells. Measuring protein function in front of an identical genetical, cellular and mitochondrial background will allow the determination of differences in UCP1 activity and regulation within Afrotherians and in comparison to modern eutherians, as well as the identification of conserved structure-function relationships.

本研究旨在进一步探讨棕色脂肪组织（BAT）及其产热蛋白解偶联蛋白-1（UCP 1）的功能以及非颤抖性适应性产热的可塑性。myurus、爱德华象（Elephantulus edwardii）、长头钝体鱼（Amblysomus hottentottus longiceps）、蓝刺头鱼（Echinops telfairi））。我们提出的项目的中心目标是揭示非洲兽产热棕色脂肪是否已经传达了推断经典非颤抖产热所需的所有目前已知的关键特征。我们的方法是缩放从体内代谢反应（迟钝的行为，能力nonshriving产热）在自由放养的动物，在不同的季节，产热的分子机制。分离的大肠杆菌BAT线粒体的分子参数和生物能量学。edwardii和E. telfairi将在体外和体内研究通过线粒体质子泄漏动力学获取产热蛋白的复杂技术。对于后者，从E. myurus、E. edwardii，A. H. longiceps和E. telfairi将被克隆并稳定转染到HEK 293（人胚肾）细胞中。在相同的遗传、细胞和线粒体背景前测量蛋白质功能将允许确定非洲兽中UCP 1活性和调节的差异，并与现代真兽相比，以及鉴定保守的结构-功能关系。

项目成果

Seasonal changes in thermogenesis of a free-ranging afrotherian small mammal, the Western rock elephant shrew (Elephantulus rupestris)

自由放养的非洲兽类小型哺乳动物西部岩象鼩（Elephantulus rupestris）产热的季节变化

• DOI: 10.1007/s00360-012-0647-x
• 发表时间: 2012
• 期刊: Journal of Comparative Physiology B
• 作者: Oelkrug R;Meyer C.W;Heldmaier G;Mzilikazi N.
• 通讯作者: Mzilikazi N.

Molecular characterization of brown adipose tissue in a ‘protoendothermic’ mammal provides a novel approach to the understanding of uncoupling protein evolution

“原吸热”哺乳动物棕色脂肪组织的分子特征为理解解偶联蛋白质进化提供了一种新方法

• DOI: 10.1016/j.bbabio.2012.06.125
• 发表时间: 2012
• 作者: Oelkrug R;Goetze N;Exner C;Ganjam G.K;Müller S;Kutschke M;Tschöp M;Heldmaier G;Jastroch M;Meyer C.W.
• 通讯作者: Meyer C.W.