UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity.
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.
Madsen
Lise
L
Department of Biology, University of Copenhagen, Copenhagen, Denmark. lise.madsen@nifes.no
Pedersen
Lone M
LM
Lillefosse
Haldis Haukaas
HH
Fjaere
Even
E
Bronstad
Ingeborg
I
Hao
Qin
Q
Petersen
Rasmus K
RK
Hallenborg
Philip
P
Ma
Tao
T
De Matteis
Rita
R
Araujo
Pedro
P
Mercader
Josep
J
Bonet
M Luisa
ML
Hansen
Jacob B
JB
Cannon
Barbara
B
Nedergaard
Jan
J
Wang
Jun
J
Cinti
Saverio
S
Voshol
Peter
P
Døskeland
Stein Ove
SO
Kristiansen
Karsten
K
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
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