Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes.
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.
Vegiopoulos
Alexandros
A
Emmy Noether and Marie Curie Research Group Molecular Metabolic Control, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.
Müller-Decker
Karin
K
Strzoda
Daniela
D
Schmitt
Iris
I
Chichelnitskiy
Evgeny
E
Ostertag
Anke
A
Berriel Diaz
Mauricio
M
Rozman
Jan
J
Hrabe de Angelis
Martin
M
Nüsing
Rolf M
RM
Meyer
Carola W
CW
Wahli
Walter
W
Klingenspor
Martin
M
Herzig
Stephan
S
D052437:Adipocytes, Brown / Q000166:cytology / Q000502:physiology*; D050156:Adipogenesis; D000273:Adipose Tissue; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000502:physiology*; D052436:Adipose Tissue, White / Q000201:enzymology / Q000502:physiology*; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D004149:Dioxoles / Q000494:pharmacology; D004734:Energy Metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D009638:Norepinephrine / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000517:prevention & control; D010101:Oxygen Consumption; D011453:Prostaglandins / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D015398:Signal Transduction; D022722:Thermogenesis
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004041:Dietary Fats; D004149:Dioxoles; D011453:Prostaglandins; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D009638:Norepinephrine