UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity

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Documents

  • Lise Madsen
  • Lone M Pedersen
  • Haldis Haukaas Lillefosse
  • Even Fjaere
  • Ingeborg Bronstad
  • Qin Hao
  • Rasmus Koefoed Petersen
  • Philip Hallenborg
  • Tao Ma
  • Rita De Matteis
  • Pedro Araujo
  • Josep Mercader
  • M Luisa Bonet
  • Barbara Cannon
  • Jan Nedergaard
  • Jun Wang
  • Saverio Cinti
  • Peter Voshol
  • Stein Ove Døskeland
BACKGROUND: The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
Original languageEnglish
JournalPLoS ONE
Volume5
Issue number6
Pages (from-to)1-13
Number of pages111,391
ISSN1932-6203
DOIs
Publication statusPublished - 30 Jan 2010

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