西亚试剂：Cyclooxygenase-2 Controls Energy Homeostasis in Mice by de

Cyclooxygenase-2 Controls Energy Homeostasis in Mice by de Novo Recruitment of Brown Adipocytes
Alexandros Vegiopoulos,1,* Karin Müller-Decker,2,* Daniela Strzoda,1 Iris Schmitt,1 Evgeny Chichelnitskiy,1 Anke Ostertag,1 Mauricio Berriel Diaz,1 Jan Rozman,3 Martin Hrabe de Angelis,3 Rolf M. Nüsing,4 Carola W. Meyer,5 Walter Wahli,6 Martin Klingenspor,7 Stephan Herzig1,

Obesity results from chronic energy surplus and excess lipid storage in white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) efficiently burns lipids through adaptive thermogenesis. Studying mouse models, we show that cyclooxygenase (COX)–2, a rate-limiting enzyme in prostaglandin (PG) synthesis, is a downstream effector of β-adrenergic signaling in WAT and is required for the induction of BAT in WAT depots. PG shifted the differentiation of defined mesenchymal progenitors toward a brown adipocyte phenotype. Overexpression of COX-2 in WAT induced de novo BAT recruitment in WAT, increased systemic energy expenditure, and protected mice against high-fat diet–induced obesity. Thus, COX-2 appears integral to de novo BAT recruitment, suggesting that the PG pathway regulates systemic energy homeostasis.

1 Emmy Noether and Marie Curie Research Group Molecular Metabolic Control, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.
2 Core Facility Tumor Models, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.
3 Institute of Experimental Genetics, Helmholtz Center Munich, 85764 Neuherberg, Germany.
4 Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, 60590 Frankfurt, Germany.
5 Department of Animal Physiology, Philipps University Marburg, 35043 Marburg, Germany.
6 Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, 1015 Lausanne, Switzerland.
7 Molecular Nutritional Medicine, Else-Kr?ner Fresenius Center, Technische Universit?t München, 85350 Freising-Weihenstephan, Germany.

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