Abstract
BackgroundObesity is a major worldwide threat to human health. Increasing evidence indicates that epigenetic modifications have a major impact on the natural history of this disorder. Ankyrin Repeat Domain 26 (Ankrd26) is involved in the development of both obesity and diabetes in mice and is modulated by environmentally induced epigenetic modifications. This study aims at investigating whether impaired ANKRD26 gene expression and methylation occur in human obesity and whether they correlate to the phenotype of these subjects.ResultsWe found that downregulation of ANKRD26 mRNA and hyper-methylation of a specific region of the ANKRD26 promoter, embedding the CpG dinucleotides − 689, − 659, and − 651 bp, occur in peripheral blood leukocytes from obese compared with the lean subjects. ANKRD26 gene expression correlates inversely to the percentage of DNA methylation at these 3 CpG sites. Luciferase assays reveal a cause-effect relationship between DNA methylation at the 3 CpG sites and ANKRD26 gene expression. Finally, both ANKRD26 mRNA levels and CpG methylation correlate to body mass index and to the pro-inflammatory status and the increased cardio-metabolic risk factors of these same subjects.ConclusionDownregulation of the ANKRD26 gene and hyper-methylation at specific CpGs of its promoter are common abnormalities in obese patients. These changes correlate to the pro-inflammatory profile and the cardio-metabolic risk factors of the obese individuals, indicating that, in humans, they mark adverse health outcomes.
Highlights
Obesity is a major worldwide threat to human health
When the study group subjects were stratified based on the TG/high-density lipoprotein cholesterol (HDL-C) ratio [24], we found that, independent of body mass index (BMI), the Ankyrin Repeat Domain 26 (ANKRD26) mRNA levels were reduced by about 60% in the individuals with the TG/HDL-C ratio > 3.0 compared with subjects with a TG/HDL-C ratio < 3.0 (BMIadjusted p = 0.016; Fig. 4c)
We found that the ANKRD26 gene expression in the blood cells correlates positively to its mRNA expression in abdominal Visceral adipose tissue (VAT), a tissue relevant to ANKRD26 protein function [14, 22, 35, 36], suggesting that perturbation of ANKRD26 expression is biologically relevant to obesity
Summary
Obesity is a major worldwide threat to human health. Increasing evidence indicates that epigenetic modifications have a major impact on the natural history of this disorder. Pfeiffer et al have demonstrated that the gene expression and DNA methylation of their candidate gene, the hypoxia-inducible factor 3A, is related to adipose tissue dysfunction, making this gene an important factor involved in the etiology of obesity [13]. Whether these associations are causal and the direction of the causations remains controversial. Whether epigenetic changes affect obesity development or vice versa still represents an open question and will need to be assessed on a case-by-case basis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
