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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:15-qucosa-222220 |
| Date | 29 March 2017 |
| Creators | Pfeiffer, Susanne |
| Contributors | Medizinische Fakultät Universität Leipzig, Klinik für Endokrinologie und Nephrologie, Professor Wieland Kiess |
| Publisher | Universitätsbibliothek Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis |
| Format | application/pdf |
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