Prostaglandin synthesis in adipose tissue from women with simple obesity. Differences between omental and subcutaneous depots

Prostanoids have been elucidated as potent adipogenic hormones. Cyclooxygenase (PTGS) is the rate-limiting enzyme of prostanoid biosynthesis and its product, prostaglandin (PG) H2 is a precursor of PGE2, PGF2, PGD2 and PGI2. PGH2 is also 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 a PPARgamma 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 PTGS1 (2.1-fold), PTGI-synthase (4.1-fold) and PTGDS (3.2-fold) in OM compared to SC tissue. Conversely, in SC tissue expression of AKR1C3 enzyme was increased (3.2-fold) compared to OM tissue. We found no difference in total PPARgamma (type 1 and type 2) expression between the different sites. This was confirmed by quantitative real-time PCR (RT-PCR). However, using RT-PCR and isoform specific primers and probe for PPARgamma2, expression of PPARgamma2 was higher in OM tissue (deltaCt 15.32 vs 17.12; p<0.001). 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 undergoing elective abdominal surgery (age range 30-50 yrs; BMI 19.7-39.2 kg/m2). Using RT-PCR, we found a significant positive correlation (p=0.012) between BMI and PTGS1 expression in SC tissue. In conclusion, the differential, depot-specific expression of key enzymes of the PG pathway may have an important impact upon fat cell biology and may help to explain depot-specific differences in adipocyte differentiation. In addition, the positive correlation between PTGS1 and BMI suggests that the regulation of PG synthesis may have a role in determining fat distribution in human obesity.