Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes

Alexandros Vegiopoulos; Karin Müller-Decker; Daniela Strzoda; Iris Schmitt; Evgeny Chichelnitskiy; Anke Ostertag; Mauricio Berriel Diaz; Jan Rozman; Martin Hrabe de Angelis; Rolf M Nüsing; Carola W Meyer; Walter Wahli; Martin Klingenspor; Stephan Herzig

doi:10.1126/science.1186034

Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes

Science. 2010 May 28;328(5982):1158-61. doi: 10.1126/science.1186034. Epub 2010 May 6.

Authors

Alexandros Vegiopoulos¹, Karin Müller-Decker, Daniela Strzoda, Iris Schmitt, Evgeny Chichelnitskiy, Anke Ostertag, Mauricio Berriel Diaz, Jan Rozman, Martin Hrabe de Angelis, Rolf M Nüsing, Carola W Meyer, Walter Wahli, Martin Klingenspor, Stephan Herzig

Affiliation

¹ Emmy Noether and Marie Curie Research Group Molecular Metabolic Control, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.

PMID: 20448152
DOI: 10.1126/science.1186034

Abstract

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 beta-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, which suggests that the PG pathway regulates systemic energy homeostasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes, Brown / cytology
Adipocytes, Brown / physiology*
Adipogenesis
Adipose Tissue
Adipose Tissue, Brown / cytology
Adipose Tissue, Brown / physiology*
Adipose Tissue, White / enzymology
Adipose Tissue, White / physiology*
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists / pharmacology
Animals
Body Weight
Cyclooxygenase 2 / genetics*
Cyclooxygenase 2 / metabolism*
Dietary Fats / administration & dosage
Dioxoles / pharmacology
Energy Metabolism*
Female
Gene Expression Regulation, Enzymologic
Homeostasis
Male
Mesenchymal Stem Cells / cytology
Mice
Mice, Inbred C57BL
Mice, Obese
Mice, Transgenic
Norepinephrine / metabolism
Obesity / etiology
Obesity / prevention & control
Oxygen Consumption
Prostaglandins / metabolism*
Receptors, Adrenergic, beta-3 / metabolism
Signal Transduction
Thermogenesis*

Substances

Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Dietary Fats
Dioxoles
Prostaglandins
Receptors, Adrenergic, beta-3
disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
Ptgs2 protein, mouse
Cyclooxygenase 2
Norepinephrine