Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue |
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Authors: | Per-arne Svensson Britt G Gabrielsson Margareta Jernås Anders Gummesson Kajsa Sjöholm |
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Institution: | (1) Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden |
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Abstract: | 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 (PPARγ). 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.
These authors contributed equally to this study |
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Keywords: | Metabolic syndrome Adipose tissue Adipocytes Diet-induced weight loss Aldoketoreductase 1C3 15-deoxy-12 14-prostaglandin J2 |
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