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PGF 2α  may be involved in the regulation of adipose tissue function.    Objectives  1) To examine PGF 2α  release by primary preadipocytes, mature adipocytes and whole tissue explants from the subcutaneous and omental fat compartments; 2) To assess which PGF synthase is the most relevant in human adipose tissue.    Methods  Fat samples were obtained by surgery in women. PGF 2α  release by preadipocytes, adipocytes and explants under stimulation by TNF-α, IL-1β or both was measured. Messenger RNA expression levels of  AKR1B1  and  AKR1C3  were measured by RT-PCR in whole adipose tissue and cytokine-treated preadipocytes. The effect of AKR1B1 inhibitor ponalrestat on PGF 2α  synthesis was investigated.    Results  PGF 2α  release was significantly induced in response to cytokines compared to control in omental (p = 0.01) and to a lesser extent in subcutaneous preadipocytes (p = 0.02). Messenger RNA of  COX-2  was significantly higher in omental compared to subcutaneous preadipocytes in response to combined TNF-α and IL-1β (p = 0.01). Inflammatory cytokines increased AKR1B1 mRNA expression and protein levels (p≤0.05), but failed to increase expression levels of  AKR1C3  in cultured preadipocytes. Accordingly, ponalrestat blunted PGF 2α  synthesis by preadipocytes in basal and stimulated conditions (p≤0.05). Women with the highest PGF 2α  release by omental adipocytes had a higher BMI (p = 0.05), waist circumference (p≤0.05) and HOMAir index (p≤0.005) as well as higher mRNA expression of  AKR1B1  in omental (p<0.10) and subcutaneous (p≤0.05) adipose tissue compared to women with low omental adipocytes PGF 2α  release. Positive correlations were observed between mRNA expression of AKR1B1 in both compartments and BMI, waist circumference as well as HOMAir index (p≤0.05 for all).    Conclusion  PGF 2α  release by omental mature adipocytes is increased in abdominally obese women. Moreover, COX-2 expression and PGF 2α  release is particularly responsive to inflammatory stimulation in omental preadipocytes. Yet, blockade of PGF synthase AKR1B1 inhibits most of the PGF 2α  release.

plos one

Prostaglandin (PG) F2 Alpha Synthesis in Human Subcutaneous and Omental Adipose Tissue: Modulation by Inflammatory Cytokines and Role of the Human Aldose Reductase AKR1B1