Abstract
BackgroundThe uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis.Methodology/Principal FindingsHere 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 β-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/SignificanceOur 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.
Highlights
The two types of adipose tissues, white (WAT) and brown (BAT), have opposite functions in whole body energy homeostasis
Real time qPCR analysis verified that genes preferentially expressed in brown vs. white adipose tissue, such as uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma coactivator 1a (PGC1a), type II thyroxine deiodinase (Dio2), cytochrome C oxidase subunit 8b (Cox8b), epithelial V like antigen 1 (Eva1) and Cidea were all highly induced in inguinal white adipose depot (iWAT) upon cold exposure, whereas expression of 4EBP1 and of nuclear receptor interacting protein 140 (Nrip1/ RIP140) was reduced (Figure 1D)
The lack of COX1 and COX2 expression in adipocytes from iBAT in warm-acclimated mice was verified by analysis of protein and RNA isolated from fractionated adipose tissue, in which COX1 and COX2 was detected solely in the stromal vascular fraction (Figure S1B)
Summary
The two types of adipose tissues, white (WAT) and brown (BAT), have opposite functions in whole body energy homeostasis. An increased content of UCP1 in adipose tissue mitochondria is strongly linked to protection against dietinduced obesity. This is true whether increased UCP1 expression is induced by transgenic expression of UCP1 itself [2;3], of forkhead box 2 (FOXC2) [4], of PR domain containing 16 (PRDM16) [5] or by disruption of the RIIb subunit of protein kinase A [6;7], eukaryotic translation initiation factor E4-binding protein 1 (4EBP1) [8], cell death inducing DFFA like effector A and C (Cidea and Cidec/Fsp27) [9], the p160 coregulator TIF2 [10] or retinoblastoma Rb [11,12,13]. The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
