TY  - JOUR
A1  - Pfeiffer, Susanne
A1  - Krüger, Jacqueline
A1  - Maierhofer, Anna
A1  - Böttcher, Yvonne
A1  - Klöting, Nora
A1  - El Hajj, Nady
A1  - Schleinitz, Dorit
A1  - Schön, Michael R.
A1  - Dietrich, Arne
A1  - Fasshauer, Mathias
A1  - Lohmann, Tobias
A1  - Dreßler, Miriam
A1  - Stumvoll, Michael
A1  - Haaf, Thomas
A1  - Blüher, Matthias
A1  - Kovacs, Peter
T1  - Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction
JF  - Scientific Reports
N2  - Recently, a genome-wide analysis identified DNA methylation of the HIF3A (hypoxia-inducible factor 3A) as strongest correlate of BMI. Here we tested the hypothesis that HIF3A mRNA expression and CpG-sites methylation in adipose tissue (AT) and genetic variants in HIF3A are related to parameters of AT distribution and function. In paired samples of subcutaneous AT (SAT) and visceral AT (VAT) from 603 individuals, we measured HIF3A mRNA expression and analyzed its correlation with obesity and related traits. In subgroups of individuals, we investigated the effects on HIF3A genetic variants on its AT expression (N = 603) and methylation of CpG-sites (N = 87). HIF3A expression was significantly higher in SAT compared to VAT and correlated with obesity and parameters of AT dysfunction (including CRP and leucocytes count). HIF3A methylation at cg22891070 was significantly higher in VAT compared to SAT and correlated with BMI, abdominal SAT and VAT area. Rs8102595 showed a nominal significant association with AT HIF3A methylation levels as well as with obesity and fat distribution. HIF3A expression and methylation in AT are fat depot specific, related to obesity and AT dysfunction. Our data support the hypothesis that HIF pathways may play an important role in the development of AT dysfunction in obesity.
KW  - gene expression
KW  - adipose
KW  - hypoxia-inducible factor 3A
KW  - adipose tissue dysfunction
KW  - obesity
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167662
VL  - 6
IS  - 27969
ER  -