title: A high-throughput, image-based screen to identify kinases involved in brown adipocyte development.
abstract: 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.
authors.affiliation: Institute of Food, Nutrition and Health, ETH-Zürich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
authors.forename: Aliki
authors.identifier: 0000-0001-6841-4187
authors.initials: A
authors.lastname: Perdikari
authors.affiliation: Institute of Food, Nutrition and Health, ETH-Zürich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kulenkampff
authors.affiliation: Institute of Food, Nutrition and Health, ETH-Zürich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
authors.forename: Carla
authors.initials: C
authors.lastname: Rudigier
authors.affiliation: Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma GmbH and Co. KG, 88397 Biberach/Riss, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Neubauer
authors.affiliation: Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma GmbH and Co. KG, 88397 Biberach/Riss, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Luippold
authors.affiliation: Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma GmbH and Co. KG, 88397 Biberach/Riss, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Redemann
authors.affiliation: Institute of Food, Nutrition and Health, ETH-Zürich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland. christian-wolfrum@ethz.ch.
authors.forename: Christian
authors.identifier: 0000-0002-3862-6805
authors.initials: C
authors.lastname: Wolfrum
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D057166:High-Throughput Screening Assays / Q000379:methods*; D051379:Mice; D010770:Phosphotransferases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D034622:RNA Interference
chemical_list: D021122:Protein Subunits; D010770:Phosphotransferases; D055372:AMP-Activated Protein Kinases