Aldoketoreductase 1C3 (AKR1C3) is a functional
prostaglandin F synthase and a negative modulator of the availability of
ligands for the
nuclear receptor peroxisome proliferator-activated receptor-gamma (
PPARgamma). AKR1C3 expression is known to be associated with adiposity, one of the components of the
metabolic syndrome. The aim of this study was to characterize the expression of AKR1C3 in the adipose tissue and adipocytes and to investigate its potential role in the
metabolic syndrome. Using microarray analysis and realtime PCR, we studied the expression of AKR1C3 in adipose tissue samples from obese subjects with or without metabolic complications, during very
low calorie diet-induced
weight loss, and its expression in isolated human adipocytes of different sizes. The adipose tissue AKR1C3 expression levels were marginally lower in obese subjects with the
metabolic syndrome compared with the levels in healthy obese subjects when analyzed using microarray (p = 0.078) and realtime PCR (p < 0.05), suggesting a secondary or compensatory effect. The adipose tissue
mRNA levels of AKR1C3 were reduced during and after dietinduced
weight-loss compared to the levels before the start of the diet (p < 0.001 at all time-points). The gene expression of AKR1C3 correlated with both adipose tissue
mRNA levels and serum levels of
leptin before the start of the diet (p < 0.05 and p < 0.01, respectively). Furthermore, large adipocytes displayed a higher expression of AKR1C3 than small adipocytes (1.5-fold, p < 0.01). In conclusion, adipose tissue AKR1C3 expression may be affected by
metabolic disease, and its levels are significantly reduced in response to dietinduced
weight loss and correlate with
leptin levels.