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 4 599-613Ämneskategorier
Biokemi och molekylärbiologi
Cell- och molekylärbiologi
DOI
10.2478/s11658-008-0025-6