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. 2022 Mar 7:9:785281.
doi: 10.3389/fnut.2022.785281. eCollection 2022.

Novel Zinc-Related Differentially Methylated Regions in Leukocytes of Women With and Without Obesity

Natália Yumi Noronha  1 , Mariana Barato  2 , Chanachai Sae-Lee  3 , Marcela Augusta de Souza Pinhel  1   2 , Lígia Moriguchi Watanabe  4 , Vanessa Aparecida Batista Pereira  4 , Guilherme da Silva Rodrigues  1 , Déborah Araújo Morais  5 , Wellington Tavares de Sousa Jr  5 , Vanessa Cristina de Oliveira Souza  5 , Jessica Rodrigues Plaça  6 , Wilson Salgado Jr  7 , Fernando Barbosa Jr  5 , Torsten Plösch  8 , Carla Barbosa Nonino  1   4
Affiliations

Novel Zinc-Related Differentially Methylated Regions in Leukocytes of Women With and Without Obesity

Natália Yumi Noronha et al. Front Nutr. .

Erratum in

Abstract

Introduction: Nutriepigenetic markers are predictive responses associated with changes in "surrounding" environmental conditions of humans, which may influence metabolic diseases. Although rich in calories, Western diets could be linked with the deficiency of micronutrients, resulting in the downstream of epigenetic and metabolic effects and consequently in obesity. Zinc (Zn) is an essential nutrient associated with distinct biological roles in human health. Despite the importance of Zn in metabolic processes, little is known about the relationship between Zn and epigenetic. Thus, the present study aimed to identify the epigenetic variables associated with Zn daily ingestion (ZnDI) and serum Zinc (ZnS) levels in women with and without obesity.

Materials and methods: This is a case-control, non-randomized, single-center study conducted with 21 women allocated into two groups: control group (CG), composed of 11 women without obesity, and study group (SG), composed of 10 women with obesity. Anthropometric measurements, ZnDI, and ZnS levels were evaluated. Also, leukocyte DNA was extracted for DNA methylation analysis using 450 k Illumina BeadChips. The epigenetic clock was calculated by Horvath method. The chip analysis methylation pipeline (ChAMP) package selected the differentially methylated regions (DMRs).

Results: The SG had lower ZnS levels than the CG. Moreover, in SG, the ZnS levels were negatively associated with the epigenetic age acceleration. The DMR analysis revealed 37 DMRs associated with ZnDI and ZnS levels. The DMR of PM20D1 gene was commonly associated with ZnDI and ZnS levels and was hypomethylated in the SG.

Conclusion: Our findings provide new information on Zn's modulation of DNA methylation patterns and bring new perspectives for understanding the nutriepigenetic mechanisms in obesity.

Keywords: DNA methylation; PM20D1; age acceleration; epigenetic markers; zinc deficiency.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) AAR: Age Acceleration Residual (measured in arbitrary units), (B) Spearman's Correlation of the serum zinc (ZnS) levels and the AAR, (C) Spearman's Correlation of the BMI and AAR, (D) Spearman's Correlation of the waist circumference (WC) and AAR.
Figure 2
Figure 2
(A) Comparison of chronological Age (in years) between study group (SG) and control group (CG), (B) Comparison of DNA methylation age (DNAm) age (in years) between SG and CG, (C) Comparison of age acceleration residual (AAR) (in years) between SG and CG (p* = 0.036).
Figure 3
Figure 3
(A) Gene Ontology Enriched Terms performed on Webgestalt Web Tool, (B) Venn Diagram of all retrieved differentially methylated regions (DMRs) from the Champ algorithm.
Figure 4
Figure 4
M values of evaluated CpG sites in DMR of PM20D1 gene in SG e CG.
Figure 5
Figure 5
Proposed interlink between Zinc status, epigenetics and obesity.
See this image and copyright information in PMC

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