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Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue

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.

Abbreviations

15d-PGJ2 :

15-deoxy-12,14-prostaglandin J2

AKR1C3:

aldoketoreductase 1C3

BMI:

body mass index

HDL:

high density lipoprotein

hs-CRP:

high sensitivity C-reactive protein

LDL:

low density lipoprotein

om:

omental

PPARγ:

peroxisome proliferator-activated receptor-gamma

sc:

subcutaneous

VLCD:

very low calorie diet

WHR:

waist-to-hip ratio

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Correspondence to Kajsa Sjöholm.

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These authors contributed equally to this study

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Svensson, Pa., Gabrielsson, B.G., Jernås, M. et al. Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue. Cell Mol Biol Lett 13, 599–613 (2008). https://doi.org/10.2478/s11658-008-0025-6

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  • DOI: https://doi.org/10.2478/s11658-008-0025-6

Key words

  • Metabolic syndrome
  • Adipose tissue
  • Adipocytes
  • Diet-induced weight loss
  • Aldoketoreductase 1C3
  • 15-deoxy-12,14-prostaglandin J2