Perdikari Aliki, Kulenkampff Elisabeth, Rudigier Carla, Neubauer Heike, Luippold Gerd, Redemann Norbert, Wolfrum Christian
Institute of Food, Nutrition and Health, ETH-Zürich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma GmbH and Co. KG, 88397 Biberach/Riss, Germany.
Sci Signal. 2017 Feb 14;10(466):eaaf5357. doi: 10.1126/scisignal.aaf5357.
Brown adipose tissue (BAT) is responsible for thermogenesis that is not associated with shivering through the process of converting chemical energy into heat through uncoupling protein 1 (UCP1) in the mitochondria. Thus, expanding or activating BAT could be a potential tool against obesity. To analyze the effect of kinase signaling on brown adipocyte formation, a process that describes the acquisition of the ability to dissipate energy as heat, we performed lentiviral-mediated short hairpin knockdown or used pharmacological inhibitors in a high-content and high-throughput in vitro image-based screen. We identified 190 kinases that either stimulated or inhibited brown adipocyte proliferation, differentiation, or formation. Among these kinases, we found that 5' AMP-activated protein kinase (AMPK) promoted the formation of brown adipocytes abundant inUCP1. Together, our results provide insight into the kinases, particularly AMPK, that regulate brown adipocyte formation.
棕色脂肪组织（BAT）通过线粒体中的解偶联蛋白1（UCP1）将化学能转化为热量，从而负责与寒战无关的产热过程。因此，增加或激活棕色脂肪组织可能是对抗肥胖的一种潜在手段。为了分析激酶信号传导对棕色脂肪细胞形成的影响（棕色脂肪细胞形成描述了将能量以热量形式消散的能力的获得过程），我们在基于体外图像的高内涵和高通量筛选中进行了慢病毒介导的短发夹RNA敲低或使用了药理学抑制剂。我们鉴定出了190种激酶，它们要么刺激要么抑制棕色脂肪细胞的增殖、分化或形成。在这些激酶中，我们发现5'单磷酸腺苷激活的蛋白激酶（AMPK）促进了富含UCP1的棕色脂肪细胞的形成。总之，我们的研究结果为调节棕色脂肪细胞形成的激酶，特别是AMPK，提供了深入见解。
