Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction

Susanne Pfeiffer; Jacqueline Krüger; Anna Maierhofer; Yvonne Böttcher; Nora Klöting; Nady El Hajj; Dorit Schleinitz; Michael R. Schön; Arne Dietrich; Mathias Fasshauer; Tobias Lohmann; Miriam Dreßler; Michael Stumvoll; Thomas Haaf; Matthias Blüher; Peter Kovacs

doi:10.1038/srep27969

Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction

Susanne Pfeiffer
, Jacqueline Krüger
, Anna Maierhofer
, Yvonne Böttcher
, Nora Klöting
, Nady El Hajj
, Dorit Schleinitz
, Michael R. Schön
, Arne Dietrich
, Mathias Fasshauer
, Tobias Lohmann
, Miriam Dreßler
, Michael Stumvoll
, Thomas Haaf
, Matthias Blüher
, Peter Kovacs^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

56 Citations (Scopus)

Abstract

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.

Original language	English
Article number	27969
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep27969
Publication status	Published - 27 Jun 2016
Externally published	Yes

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10.1038/srep27969

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Pfeiffer, S., Krüger, J., Maierhofer, A., Böttcher, Y., Klöting, N., El Hajj, N., Schleinitz, D., Schön, M. R., Dietrich, A., Fasshauer, M., Lohmann, T., Dreßler, M., Stumvoll, M., Haaf, T., Blüher, M., & Kovacs, P. (2016). Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction. Scientific Reports, 6, Article 27969. https://doi.org/10.1038/srep27969

@article{56717780e90c4fa8aedad9faa4a56dd7,

title = "Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction",

abstract = "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.",

author = "Susanne Pfeiffer and Jacqueline Kr{\"u}ger and Anna Maierhofer and Yvonne B{\"o}ttcher and Nora Kl{\"o}ting and \{El Hajj\}, Nady and Dorit Schleinitz and Sch{\"o}n, \{Michael R.\} and Arne Dietrich and Mathias Fasshauer and Tobias Lohmann and Miriam Dre{\ss}ler and Michael Stumvoll and Thomas Haaf and Matthias Bl{\"u}her and Peter Kovacs",

year = "2016",

month = jun,

day = "27",

doi = "10.1038/srep27969",

language = "English",

volume = "6",

journal = "Scientific Reports",

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Pfeiffer, S, Krüger, J, Maierhofer, A, Böttcher, Y, Klöting, N, El Hajj, N, Schleinitz, D, Schön, MR, Dietrich, A, Fasshauer, M, Lohmann, T, Dreßler, M, Stumvoll, M, Haaf, T, Blüher, M & Kovacs, P 2016, 'Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction', Scientific Reports, vol. 6, 27969. https://doi.org/10.1038/srep27969

TY - JOUR

T1 - Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction

AU - Pfeiffer, Susanne

AU - Krüger, Jacqueline

AU - Maierhofer, Anna

AU - Böttcher, Yvonne

AU - Klöting, Nora

AU - El Hajj, Nady

AU - Schleinitz, Dorit

AU - Schön, Michael R.

AU - Dietrich, Arne

AU - Fasshauer, Mathias

AU - Lohmann, Tobias

AU - Dreßler, Miriam

AU - Stumvoll, Michael

AU - Haaf, Thomas

AU - Blüher, Matthias

AU - Kovacs, Peter

PY - 2016/6/27

Y1 - 2016/6/27

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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84976629789

U2 - 10.1038/srep27969

DO - 10.1038/srep27969

M3 - Article

C2 - 27346320

AN - SCOPUS:84976629789

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 27969

ER -

Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction

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