Cyclooxygenase-2 deficiency attenuates adipose tissue differentiation and inflammation in mice.
Obesity is associated with a variety of disorders and is a significant health problem in developed countries. One factor controlling the level of adiposity is the differentiation of cells into adipocytes. Adipocyte differentiation requires expression of peroxisome proliferator-activated receptor γ (PPARγ), which is activated by ligands to regulate expression of genes involved in adipocyte differentiation. Although 15-deoxy-Δ(12,14)-prostaglandin (PG) J(2) (15d-PGJ(2)) has long been known to be a potent activator of PPARγ, the importance of its synthesis in adipose tissue in vivo is not clear. The current study utilized mice deficient in cyclooxygenase-2 (COX-2) to examine the role of COX-2-derived PGs as in vivo modulators of adiposity. As compared with strain- and age-matched wild-type controls, the genetic deficiency of COX-2 resulted in a significant reduction in total body weight and percent body fat. Although there were no significant differences in food consumption between groups, COX-2-deficient mice showed increased metabolic activity. Epididymal adipose tissue from wild-type mice produced a significantly greater level of 15d-PGJ(2), as compared with adipose tissue isolated from mice deficient in COX-2. Furthermore, production of the precursor required for 15d-PGJ(2) formation, PGD(2), was also significantly reduced in COX-2-deficient adipose tissue. The expression of markers for differentiated adipocytes was significantly reduced in adipose tissue from COX-2-deficient mice, whereas preadipocyte marker expression was increased. Macrophage-dependent inflammation was also significantly reduced in adipose tissue of COX-2-deficient mice. These findings suggest that reduced adiposity in COX-2-deficient mice results from attenuated PPARγ ligand production and adipocyte differentiation.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA.
Sarbani
S
Ghoshal
Darshini B
DB
Trivedi
Gregory A
GA
Graf
Charles D
CD
Loftin
D052438:Adipocytes, White / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000235:genetics; D007249:Inflammation / Q000201:enzymology; D008297:Male; D051379:Mice; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism
D015415:Biomarkers; D011453:Prostaglandins; D051546:Cyclooxygenase 2