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

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

doi:10.3389/fnut.2022.785281

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

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

Authors

Natália Yumi Noronha¹, Mariana Barato², Chanachai Sae-Lee³, Marcela Augusta de Souza Pinhel^{1

2}, Lígia Moriguchi Watanabe⁴, Vanessa Aparecida Batista Pereira⁴, Guilherme da Silva Rodrigues¹, Déborah Araújo Morais⁵, Wellington Tavares de Sousa Jr⁵, Vanessa Cristina de Oliveira Souza⁵, Jessica Rodrigues Plaça⁶, Wilson Salgado Jr⁷, Fernando Barbosa Jr⁵, Torsten Plösch⁸, Carla Barbosa Nonino^{1

4}

Affiliations

¹ Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, São Paulo, Brazil.
² Department of Molecular Biology, São José do Rio Preto Medical School, São Paulo, Brazil.
³ Research Division, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
⁴ Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
⁵ Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
⁶ National Institute of Science and Technology in Stem Cell and Cell Therapy and Center for Cell-Based Therapy, São Paulo, Brazil.
⁷ Department of Surgery and Anatomy, Ribeirao Preto Medical School, São Paulo, Brazil.
⁸ Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

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.