INTRODUCTION: PGF2a may be involved in the regulation of adipose tissue function. OBJECTIVES: 1) To examine PGF2a 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. PGF2a release by preadipocytes, adipocytes and explants under stimulation by TNF-a, IL-1ß 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 PGF2a synthesis was investigated. RESULTS: PGF2a 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-a and IL-1ß (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 PGF2a synthesis by preadipocytes in basal and stimulated conditions (p=0.05). Women with the highest PGF2a 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 PGF2a 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: PGF2a release by omental mature adipocytes is increased in abdominally obese women. Moreover, COX-2 expression and PGF2a release is particularly responsive to inflammatory stimulation in omental preadipocytes. Yet, blockade of PGF synthase AKR1B1 inhibits most of the PGF2a release