title: UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity.
abstract: BACKGROUND
  The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis.
  
  
  RESULTS
  Here we report that cyclooxygenase (COX) activity and prostaglandin E(2) (PGE(2)) are crucially involved in induction of UCP1 expression in inguinal white adipocytes, but not in classic interscapular brown adipocytes. Cold-induced expression of UCP1 in inguinal white adipocytes was repressed in COX2 knockout (KO) mice and by administration of the COX inhibitor indomethacin in wild-type mice. Indomethacin repressed beta-adrenergic induction of UCP1 expression in primary inguinal adipocytes. The use of PGE(2) receptor antagonists implicated EP(4) as a main PGE(2) receptor, and injection of the stable PGE(2) analog (EP(3/4) agonist) 16,16 dm PGE(2) induced UCP1 expression in inguinal white adipose tissue. Inhibition of COX activity attenuated diet-induced UCP1 expression and increased energy efficiency and adipose tissue mass in obesity-resistant mice kept at thermoneutrality.
  
  
  CONCLUSIONS
  Our findings provide evidence that induction of UCP1 expression in white adipose tissue, but not in classic interscapular brown adipose tissue is dependent on cyclooxygenase activity. Our results indicate that cyclooxygenase-dependent induction of UCP1 expression in white adipose tissues is important for diet-induced thermogenesis providing support for a surprising role of COX activity in the control of energy balance and obesity development.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark. lise.madsen@nifes.no
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.forename: Lone M
authors.initials: LM
authors.lastname: Pedersen
authors.forename: Haldis Haukaas
authors.initials: HH
authors.lastname: Lillefosse
authors.forename: Even
authors.initials: E
authors.lastname: Fjaere
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Bronstad
authors.forename: Qin
authors.initials: Q
authors.lastname: Hao
authors.forename: Rasmus K
authors.initials: RK
authors.lastname: Petersen
authors.forename: Philip
authors.initials: P
authors.lastname: Hallenborg
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Rita
authors.initials: R
authors.lastname: De Matteis
authors.forename: Pedro
authors.initials: P
authors.lastname: Araujo
authors.forename: Josep
authors.initials: J
authors.lastname: Mercader
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Bonet
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Hansen
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Peter
authors.initials: P
authors.lastname: Voshol
authors.forename: Stein Ove
authors.initials: SO
authors.lastname: Døskeland
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007473:Ion Channels / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D016861:Cyclooxygenase Inhibitors; D007473:Ion Channels; D024101:Mitochondrial Proteins; D016160:Retinoblastoma Protein; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D051546:Cyclooxygenase 2; D007213:Indomethacin