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Madsen, L., L.M. Pedersen, H.H. Lillefosse, E. Fjære, I. Bronstad, Q. Hao, R.K. Petersen, P. Hallenborg, T. Ma, R. De Matteis, P. Araujo, J. Mercader, M.L. Bonet, J.B. Hansen, B. Cannon, J. Nedergaard, J. Wang, S. Cinti, P. Voshol, S.O. Døskeland and K. Kristiansen. 2010. UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity. PLoS ONE. 5(6):e11391.


DOI: 10.1371/journal.pone.0011391

Type of document: Journal Article

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More information on authors/freelancers connected to LBI :
Peter Voshol, PhD


Language of document: English

Title in English: UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity

Abstract / summary in English:

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 E2 (PGE2) 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 b-adrenergic induction of UCP1 expression in primary inguinal adipocytes. The use of PGE2 receptor antagonists implicated EP4 as a main PGE2 receptor, and injection of the stable PGE2 analog (EP3/4 agonist) 16,16 dm PGE2 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.


Keywords in English: uncoupling protein, cold- and diet-induced thermogenesis, cyclooxygenase (COX), prostaglandin E2, energy balance and obesity development, Type 2 Diabetes, Metabolic Syndrome, Pre-diabetes
UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity