| First Author | Ghoshal S | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 1 | Pages | 889-98 |
| PubMed ID | 20961858 | Mgi Jnum | J:167576 |
| Mgi Id | MGI:4868559 | Doi | 10.1074/jbc.M110.139139 |
| Citation | Ghoshal S, et al. (2011) Cyclooxygenase-2 deficiency attenuates adipose tissue differentiation and inflammation in mice. J Biol Chem 286(1):889-98 |
| abstractText | 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 gamma (PPARgamma), which is activated by ligands to regulate expression of genes involved in adipocyte differentiation. Although 15-deoxy-Delta(12,14)-prostaglandin (PG) J(2) (15d-PGJ(2)) has long been known to be a potent activator of PPARgamma, 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 PPARgamma ligand production and adipocyte differentiation. |
