DNA 5-Hydroxymethylation in Human Adipose Tissue Differs Between Subcutaneous and Visceral Adipose Tissue Depots

Abstract

Background: A stable intermediate during DNA demethylation, 5-hydroxymethylcytosine (5-hmC), raises questions about its function and distribution. Therefore, we tested whether 5-hmC exists in human adipose tissue depots and correlates with clinical variables. Materials & methods: We measured the % 5-hmC content in both subcutaneous adipose tissue and visceral adipose tissue (VAT) from 81 individuals by using ELISA technology. To test for associations with several clinical variables we used paired students t-tests and linear regression analyses. Results: We observed an average % 5-hmC content of 0.47% ± 0.093 in subcutaneous adipose tissue, while VAT (0.51% ± 0.122) is higher hydroxymethylated (p = 0.005). In the total cohort we observed a positive association of % 5-hmC in VAT with age (p = 0.034) and a negative relationship with low density lipoprotein-cholesterol (p = 0.008). Conclusion: Our data suggest adipose tissue depot specific 5-hmC levels with higher levels in VAT.

Keywords::

• 5-hydroxymethylation
• epigenetics
• fat distribution
• obesity
• subcutaneous fat
• visceral fat

Acknowledgements

The authors thank all those who participated in the studies. The authors are grateful to M Hankir for English language editing.

Author contributions

The study was designed by K Rohde and Y Böttcher. Results were interpreted by K Rohde, M Keller, M Blüher, M Stumvoll and Y Böttcher. Subject ascertainment and recruitment was carried out by Arne Dietrich and M Blüher. Clinical characterization and phenotyping as well as supervising the adipose tissue bio bank samples was done by M Blüher Laboratory experiments were performed by K Rohde. Authors K Rohde and Y Böttcher drafted the manuscript. All authors contributed to the final version of the paper.

Financial & competing interest disclosure

This work was supported by grants from the German Diabetes Association (to Y Böttcher) and from the DDS Foundation to Y Böttcher. Y Böttcher was further supported by a research grant from the IFB Adiposity Diseases ADI-K50D, K7-37, K7-45 and by a research fellowship from the EFSD (European Foundation for the Study of Diabetes). K Rohde was supported by ADI-K60E. IFB Adiposity Diseases is supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001. This work was further supported by the Kompetenznetz Adipositas (Competence network for Obesity) funded by the Federal Ministry of Education and Research (German Obesity Biomaterial Bank; FKZ 01GI1128), a grant from German Research Foundation, the SFB 1052/1: ‘Obesity mechanisms’ (projects A01 to M Stumvoll and B01 to M Blüher) and a research grant BO 3147/4–1 to Y Böttcher. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate insti­tutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by grants from the German Diabetes Association (to Y Böttcher) and from the DDS Foundation to Y Böttcher. Y Böttcher was further supported by a research grant from the IFB Adiposity Diseases ADI-K50D, K7-37, K7-45 and by a research fellowship from the EFSD (European Foundation for the Study of Diabetes). K Rohde was supported by ADI-K60E. IFB Adiposity Diseases is supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001. This work was further supported by the Kompetenznetz Adipositas (Competence network for Obesity) funded by the Federal Ministry of Education and Research (German Obesity Biomaterial Bank; FKZ 01GI1128), a grant from German Research Foundation, the SFB 1052/1: ‘Obesity mechanisms’ (projects A01 to M Stumvoll and B01 to M Blüher) and a research grant BO 3147/4–1 to Y Böttcher. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.