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Genetics and Epigenetics

DNA methylation in adipocytes from visceral and subcutaneous adipose tissue influences insulin-signaling gene expression in obese individuals

International Journal of Obesity volume 45, pages 650–658 (2021)Cite this article

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Abstract

Objective

Both obesity and insulin resistance are characterized by severe long-term changes in the expression of many genes of importance in the regulation of metabolism. Because these changes occur throughout life, as a result of external factors, the disorders of gene expression could be epigenetically regulated.

Materials/methods

We analyzed the relationship between obesity and insulin resistance in enrolled patients by means of evaluation of the expression rate of numerous genes involved in the regulation of adipocyte metabolism and energy homeostasis in subcutaneous and visceral adipose tissue depots. We also investigated global and site-specific DNA methylation as one of the main regulators of gene expression. Visceral and subcutaneous adipose tissue biopsies were collected from 45 patients during abdominal surgery in an age range of 40–60 years.

Results

We demonstrated hypermethylation of PPARG, INSR, SLC2A4, and ADIPOQ promoters in obese patients with insulin resistance. Moreover, the methylation rate showed a negative correlation with the expression of the investigated genes. More, we showed a correlation between the expression of PPARG and the expression of numerous genes important for proper insulin action. Given the impact of PPARγ on the regulation of the cell insulin sensitivity through modulation of insulin pathway genes expression, hypermethylation in the PPARG promoter region may constitute one of the epigenetic pathways in the development of insulin resistance in obesity.

Conclusions

Our research shows that epigenetic regulation through excessive methylation may constitute a link between obesity and subsequent insulin resistance.

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Fig. 1: A correlation between BMI and the expression level of genes with a p value.
Fig. 2: The results of the comparative analysis regarding the expression of DNMT1 gene and global DNA methylation level between three groups (LH, OH, and OR).
Fig. 3: The results of the analysis regarding to the site-specific methylation of the promoter region of the selected genes.
Fig. 4: A correlation between the expression of PPARG and the expression of other genes with a p value.

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Acknowledgements

The project was funded by The National Science Centre, Poland. The number of the research project: 2016/21/D/NZ5/00155.

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Authors and Affiliations

  1. Department of Forensic Medicine, Molecular Techniques Unit, Wroclaw Medical University, Curie-Sklodowskiej 52, 50-369, Wroclaw, Poland

    Aneta Cierzniak, Tadeusz Dobosz & Malgorzata Malodobra-Mazur

  2. Department and Division of Surgical Didactics, Wroclaw Medical University, M. Curie-Sklodowskiej 66, 50-369, Wroclaw, Poland

    Dorota Pawelka

  3. Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland

    Krzysztof Kaliszewski & Jerzy Rudnicki

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  1. Aneta Cierzniak
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Correspondence to Aneta Cierzniak.

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Cierzniak, A., Pawelka, D., Kaliszewski, K. et al. DNA methylation in adipocytes from visceral and subcutaneous adipose tissue influences insulin-signaling gene expression in obese individuals. Int J Obes 45, 650–658 (2021). https://doi.org/10.1038/s41366-020-00729-7

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