Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue.
Artikel i vetenskaplig tidskrift, 2008

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.

androgen inactivation

Oligonucleotide Array Sequence Analysis

receptor

adipocytes

Molecular Sequence Data

Metabolic Syndrome X

Humans

Adult

Female

Hydroxyprostaglandin Dehydrogenases

physiology

cytology

therapy

Weight Loss

adipogenesis

genetics

men

Gene Expression Profiling

Enzymologic

3-Hydroxysteroid Dehydrogenases

Male

Reducing

metabolism

Adipose Tissue

obese subjects

Middle Aged

genetics

weight-loss

Diet

Obesity

metabolism

Gene Expression Regulation

blood

metabolism

insulin-resistance

metabolism

Tissue Distribution

Leptin

enzymology

metabolic syndrome

body-fat distribution

Författare

Per-Arne Svensson

Göteborgs universitet

Britt Gabrielsson

Göteborgs universitet

Margareta Jernås

Göteborgs universitet

Anders Gummesson

Göteborgs universitet

Kajsa Sjöholm

Göteborgs universitet

Cellular and Molecular Biology Letters

1425-8153 (ISSN) 1689-1392 (eISSN)

Vol. 13 4 599-613

Ämneskategorier

Biokemi och molekylärbiologi

Cell- och molekylärbiologi

DOI

10.2478/s11658-008-0025-6