Prostaglandin synthesis in adipose tissue from women with simple obesity reveals characteristic differences between omental and subcutaneous fat depots

Prostanoids have been elucidated as potent adipogenic hormones. Cyclooxygenase (PTGS) is the rate-limiting enzyme of prostanoid biosynthesis. Its product, prostaglandin (PG) H2 is metabolised by prostaglandin D-synthase (PTGDS) to PGD2, which spontaneously converts to PGJ2 or can be enzymatically converted to PGF2alpha by AKR1C3. These two metabolites have opposite effect on adipogenesis: PGF2alpha is a PPARgamma antagonist where as PGJ2 is an agonist. In light of the diverse role of prostanoids in adipogenesis we examined expression of these enzymes in human subcutaneous (SC) and omental (OM) adipose tissue. Using Affymetrix cDNA microarray technique, we observed significantly higher expressions of PTGS (2.1-fold) and PTGDS (3.2-fold) in OM compared to SC tissue. Conversely, expression of AKR1C3 was increased (3.2-fold) in SC tissue compared to OM. We found no difference in total PPARgamma (type 1 and type 2) expression between the different sites, but expression of PPARgamma2 was significantly higher in OM tissue. This was confirmed by quantitative real-time PCR (RT-PCR). In a further study, we examined gene expression of PG pathways in relation to BMI. Paired OM and SC fat biopsies were obtained from 19 women (age range 30–50yrs; BMI 19.7–39.2). Using RT-PCR, we found a significant positive correlation between BMI and PTGS1 expression in SC tissue. H&E staining showed larger adipocyte diameters in SC than in OM depots. In addition, adipocyte diameter positively correlated with BMI in both depots. In conclusion, the differential, depot-specific expression of key enzymes involved in synthesis and metabolism of PG may have an important impact upon fat cell biology and may help to explain observed depot-specific differences in adipocyte differentiation. In addition, the positive correlation between PTGS1 and BMI offers the novel hypothesis that the regulation of PG synthesis may be a key determinant of fat distribution in human obesity.