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Epigenetic Mechanisms of Environmental Diseases

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 39870

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Special Issue Editors

Dr. Paola Ungaro

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Guest Editor

Istituto per l’Endocrinologia ed l’Oncologia Sperimentale 'G. Salvatore',Consiglio Nazionale delle Ricerche, Napoli, Italy
Interests: epigenetics; regulation of gene expression; obesity; adipogenesis; regulation of adipogenesis by histone-modifying enzymes; regulation of adipogenesis by polyphenols; molecular mechanisms of « browning »

Dr. Raffaele Teperino

E-Mail Website
Co-Guest Editor

Head of the Environmental Epigenetics Group, Institute of Experimental Genetics, Helmholtz Zentrum München GmbH, Neuherberg, Germany
Interests: gene/environment interaction; non-genetic inheritance; complex diseases; diabetes; obesity; cancer; epigenetics

Special Issue Information

Dear Colleagues,

This Special Issue, “Epigenetic Mechanisms of Environmental Diseases” will mainly focus on environmental influences on human health.

The human genome encodes approximately 30,000 genes. It is estimated that over 8,000 human diseases are caused by defects in single genes. These unifactorial or monogenic diseases are individually rare and affect approximately one percent of the human population. In contrast, complex human diseases such as cancer and type 2 diabetes are believed to involve both susceptibility genes and their interactions with the environment. Gene-environment interactions are thought to be mediated by epigenetic modifications across the genome that represent orchestrated phenomena which modulate the transcriptional output of the genetic code. In this sense, identifying the aberrant changes in the epigenetic landscape associated with environmental diseases such as type 2 diabetes, obesity, cancer and cardiovascular, neurodegenerative and immunological diseases could provide the potential for new approaches for disease prevention and intervention.

We cordially invite authors in the field to submit original research or review articles pertaining to this important and fast-progressing field of biomedicine.

Dr. Paola Ungaro
Guest Editor
Dr. Raffaele Teperino
Co-Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Environmental and health
Epigenetics
Cardiovascular diseases
Carcinogenesis
Infertility
Metabolic syndrome
Obesity

Published Papers (11 papers)

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Research

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15 pages, 316 KiB

Open AccessArticle

DNA Hypomethylation as a Potential Link between Excessive Alcohol Intake and Cardiometabolic Dysfunction in Morbidly Obese Adults

by Imaduddin Mirza, Dina Naquiallah, Ariej Mohamed, Uzma Abdulbaseer, Chandra Hassan, Mario Masrur, Mohamed M. Ali, Shane A. Phillips and Abeer M. Mahmoud

Biomedicines 2022, 10(8), 1954; https://doi.org/10.3390/biomedicines10081954 - 12 Aug 2022

Viewed by 1372

Abstract

A large percentage of obese patients in the United States suffer a comorbid substance use disorder, mainly alcohol use. Alcohol consumption interferes with the absorption of dietary methyl donors such as folate required for the one-carbon metabolism pathway and subsequently for DNA methylation. In this study, we assessed the association between alcohol consumption and DNA methylation in obese subjects. We obtained visceral adipose tissue (VAT) biopsies from bariatric patients. DNA methylation of 94 genes implicated in inflammation and immunity were analyzed in VAT in relation to alcohol consumption data obtained via questionnaires. Vasoreactivity was measured in the brachial artery and the VAT-isolated arterioles. Pro-inflammatory genes were significantly hypomethylated in the heavy drinking category correlating with higher levels of circulating inflammatory cytokines. Alcohol consumption correlated positively with body mass index (BMI), fat percentage, insulin resistance, impaired lipid profile, and systemic inflammation and negatively with plasma folate and vitamin B12, inflammatory gene DNA methylation, and vasoreactivity. In conclusion, these data suggest that alcohol intake is associated with lower DNA methylation and higher inflammation and cardiometabolic risk in obese individuals. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

13 pages, 25844 KiB

Open AccessArticle

Genome Profiling of H3k4me3 Histone Modification in Human Adipose Tissue during Obesity and Insulin Resistance

by Daniel Castellano-Castillo, Bruno Ramos-Molina, Wilfredo Oliva-Olivera, Luis Ocaña-Wilhelmi, María Isabel Queipo-Ortuño and Fernando Cardona

Biomedicines 2021, 9(10), 1363; https://doi.org/10.3390/biomedicines9101363 - 30 Sep 2021

Cited by 5 | Viewed by 2420

Abstract

Background: Adipose tissue (AT) dysfunction is involved in obesity-related comorbidities. Epigenetic alterations have been recently associated with AT deterioration in obesity conditions. In this work, we profiled the H3K4me3 histone mark in human AT, with special emphasis on the changes in the pattern of histone modification in obesity and insulin resistance (IR). Visceral AT (VAT) was collected and subjected to chromatin immunoprecipitation (ChIP) using anti-H3K4me3 antibody and then sequenced to obtain the H3K4me3 genome profile. Results: We found that most of the H3K4me3 enriched regions were located in gene promoters of pathways related to AT biology and function. H3K4me3 enrichment at gene promoters was strongly related to higher mRNA levels. Differentially expressed genes in AT of patients classified as non-obese, obese with low IR, and obese with high IR could be regulated by differentially enriched H3K4me3; these genes encoded for pathways that could in part explain AT functioning during obesity and insulin resistance (e.g., extracellular matrix organization, PPARG signaling or inflammation). Conclusions: In conclusion, we emphasize the importance of the epigenetic mark H3K4me3 in VAT dysfunction in obesity and IR. The understanding of such mechanisms could give rise to the development of new epigenetic-based pharmacological strategies to ameliorate obesity-related comorbidities. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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24 pages, 25001 KiB

Open AccessArticle

Adipose Tissue Hypoxia Correlates with Adipokine Hypomethylation and Vascular Dysfunction

by Mohamed M. Ali, Chandra Hassan, Mario Masrur, Francesco M. Bianco, Dina Naquiallah, Imaduddin Mirza, Patrice Frederick, Eduardo T. Fernandes, Cristoforo P. Giulianotti, Antonio Gangemi, Shane A. Phillips and Abeer M. Mahmoud

Biomedicines 2021, 9(8), 1034; https://doi.org/10.3390/biomedicines9081034 - 18 Aug 2021

Cited by 7 | Viewed by 2119

Abstract

Obesity is characterized by the accumulation of dysfunctional adipose tissues, which predisposes to cardiometabolic diseases. Our previous in vitro studies demonstrated a role of hypoxia in inducing adipokine hypomethylation in adipocytes. We sought to examine this mechanism in visceral adipose tissues (VATs) from obese individuals and its correlation with cardiometabolic risk factors. We propose an involvement of the hypoxia-inducible factor, HIF1α, and the DNA hydroxymethylase, TET1. Blood samples and VAT biopsies were obtained from obese and non-obese subjects (n = 60 each) having bariatric and elective surgeries, respectively. The analyses of VAT showed lower vascularity, and higher levels of HIF1α and TET1 proteins in the obese subjects than controls. Global hypomethylation and hydroxymethylation were observed in VAT from obese subjects along with promoter hypomethylation of several pro-inflammatory adipokines. TET1 protein was enriched near the promotor of the hypomethylated adipokines. The average levels of adipokine methylation correlated positively with vascularity and arteriolar vasoreactivity and negatively with protein levels of HIF1α and TET1 in corresponding VAT samples, serum and tissue inflammatory markers, and other cardiometabolic risk factors. These findings suggest a role for adipose tissue hypoxia in causing epigenetic alterations, which could explain the increased production of adipocytokines and ultimately, vascular dysfunction in obesity. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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Review

Jump to: Research

26 pages, 1170 KiB

Open AccessReview

Evolutionary Implications of Environmental Toxicant Exposure

by Giorgia Bolognesi, Maria Giulia Bacalini, Chiara Pirazzini, Paolo Garagnani and Cristina Giuliani

Biomedicines 2022, 10(12), 3090; https://doi.org/10.3390/biomedicines10123090 - 01 Dec 2022

Viewed by 1974

Abstract

Homo sapiens have been exposed to various toxins and harmful compounds that change according to various phases of human evolution. Population genetics studies showed that such exposures lead to adaptive genetic changes; while observing present exposures to different toxicants, the first molecular mechanism that confers plasticity is epigenetic remodeling and, in particular, DNA methylation variation, a molecular mechanism proposed for medium-term adaptation. A large amount of scientific literature from clinical and medical studies revealed the high impact of such exposure on human biology; thus, in this review, we examine and infer the impact that different environmental toxicants may have in shaping human evolution. We first describe how environmental toxicants shape natural human variation in terms of genetic and epigenetic diversity, and then we describe how DNA methylation may influence mutation rate and, thus, genetic variability. We describe the impact of these substances on biological fitness in terms of reproduction and survival, and in conclusion, we focus on their effect on brain evolution and physiology. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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21 pages, 778 KiB

Open AccessReview

The Legacy of Parental Obesity: Mechanisms of Non-Genetic Transmission and Reversibility

by Gemma Comas-Armangue, Lela Makharadze, Melisa Gomez-Velazquez and Raffaele Teperino

Biomedicines 2022, 10(10), 2461; https://doi.org/10.3390/biomedicines10102461 - 01 Oct 2022

Cited by 4 | Viewed by 2263

Abstract

While a dramatic increase in obesity and related comorbidities is being witnessed, the underlying mechanisms of their spread remain unresolved. Epigenetic and other non-genetic mechanisms tend to be prominent candidates involved in the establishment and transmission of obesity and associated metabolic disorders to offspring. Here, we review recent findings addressing those candidates, in the context of maternal and paternal influences, and discuss the effectiveness of preventive measures. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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18 pages, 641 KiB

Open AccessReview

On the Relationship between Diabetes and Obstructive Sleep Apnea: Evolution and Epigenetics

by N. R. C. Wilson, Olivia J. Veatch and Steven M. Johnson

Biomedicines 2022, 10(3), 668; https://doi.org/10.3390/biomedicines10030668 - 14 Mar 2022

Cited by 2 | Viewed by 2908

Abstract

This review offers an overview of the relationship between diabetes, obstructive sleep apnea (OSA), obesity, and heart disease. It then addresses evidence that the traditional understanding of this relationship is incomplete or misleading. In the process, there is a brief discussion of the evolutionary rationale for the development and retention of OSA in light of blood sugar dysregulation, as an adaptive mechanism in response to environmental stressors, followed by a brief overview of the general concepts of epigenetics. Finally, this paper presents the results of a literature search on the epigenetic marks and changes in gene expression found in OSA and diabetes. (While some of these marks will also correlate with obesity and heart disease, that is beyond the scope of this project). We conclude with an exploration of alternative explanations for the etiology of these interlinking diseases. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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31 pages, 3635 KiB

Open AccessReview

The Epigenetics of Psychosis: A Structured Review with Representative Loci

by Christine L. Miller

Biomedicines 2022, 10(3), 561; https://doi.org/10.3390/biomedicines10030561 - 28 Feb 2022

Cited by 4 | Viewed by 3916

Abstract

The evidence for an environmental component in chronic psychotic disorders is strong and research on the epigenetic manifestations of these environmental impacts has commenced in earnest. In reviewing this research, the focus is on three genes as models for differential methylation, MCHR1, AKT1 and TDO2, each of which have been investigated for genetic association with psychotic disorders. Environmental factors associated with psychotic disorders, and which interact with these model genes, are explored in depth. The location of transcription factor motifs relative to key methylation sites is evaluated for predicted gene expression results, and for other sites, evidence is presented for methylation directing alternative splicing. Experimental results from key studies show differential methylation: for MCHR1, in psychosis cases versus controls; for AKT1, as a pre-existing methylation pattern influencing brain activation following acute administration of a psychosis-eliciting environmental stimulus; and for TDO2, in a pattern associated with a developmental factor of risk for psychosis, in all cases the predicted expression impact being highly dependent on location. Methylation induced by smoking, a confounding variable, exhibits an intriguing pattern for all three genes. Finally, how differential methylation meshes with Darwinian principles is examined, in particular as it relates to the “flexible stem” theory of evolution. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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29 pages, 1077 KiB

Open AccessReview

Impact of Physical Activity and Exercise on the Epigenome in Skeletal Muscle and Effects on Systemic Metabolism

by Julio Plaza-Diaz, David Izquierdo, Álvaro Torres-Martos, Aiman Tariq Baig, Concepción M. Aguilera and Francisco Javier Ruiz-Ojeda

Biomedicines 2022, 10(1), 126; https://doi.org/10.3390/biomedicines10010126 - 07 Jan 2022

Cited by 17 | Viewed by 9379

Abstract

Exercise and physical activity induces physiological responses in organisms, and adaptations in skeletal muscle, which is beneficial for maintaining health and preventing and/or treating most chronic diseases. These adaptations are mainly instigated by transcriptional responses that ensue in reaction to each individual exercise, either resistance or endurance. Consequently, changes in key metabolic, regulatory, and myogenic genes in skeletal muscle occur as both an early and late response to exercise, and these epigenetic modifications, which are influenced by environmental and genetic factors, trigger those alterations in the transcriptional responses. DNA methylation and histone modifications are the most significant epigenetic changes described in gene transcription, linked to the skeletal muscle transcriptional response to exercise, and mediating the exercise adaptations. Nevertheless, other alterations in the epigenetics markers, such as epitranscriptomics, modifications mediated by miRNAs, and lactylation as a novel epigenetic modification, are emerging as key events for gene transcription. Here, we provide an overview and update of the impact of exercise on epigenetic modifications, including the well-described DNA methylations and histone modifications, and the emerging modifications in the skeletal muscle. In addition, we describe the effects of exercise on epigenetic markers in other metabolic tissues; also, we provide information about how systemic metabolism or its metabolites influence epigenetic modifications in the skeletal muscle. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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15 pages, 1041 KiB

Open AccessReview

Epigenetic Mechanisms of Endocrine-Disrupting Chemicals in Obesity

by Immacolata Cristina Nettore, Fabiana Franchini, Giuseppe Palatucci, Paolo Emidio Macchia and Paola Ungaro

Biomedicines 2021, 9(11), 1716; https://doi.org/10.3390/biomedicines9111716 - 18 Nov 2021

Cited by 16 | Viewed by 4028

Abstract

The incidence of obesity has dramatically increased over the last decades. Recently, there has been a growing interest in the possible association between the pandemics of obesity and some endocrine-disrupting chemicals (EDCs), termed “obesogens”. These are a heterogeneous group of exogenous compounds that can interfere in the endocrine regulation of energy metabolism and adipose tissue structure. Oral intake, inhalation, and dermal absorption represent the major sources of human exposure to these EDCs. Recently, epigenetic changes such as the methylation of cytosine residues on DNA, post-translational modification of histones, and microRNA expression have been considered to act as an intermediary between deleterious effects of EDCs and obesity development in susceptible individuals. Specifically, EDCs exposure during early-life development can detrimentally affect individuals via inducing epigenetic modifications that can permanently change the epigenome in the germline, enabling changes to be transmitted to the next generations and predisposing them to a multitude of diseases. The purpose of this review is to analyze the epigenetic alterations putatively induced by chemical exposures and their ability to interfere with the control of energy metabolism and adipose tissue regulation, resulting in imbalances in the control of body weight, which can lead to obesity. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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18 pages, 706 KiB

Open AccessReview

Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

by Mohamed Zaiou, Rim Amrani, Bertrand Rihn and Tahar Hajri

Biomedicines 2021, 9(9), 1256; https://doi.org/10.3390/biomedicines9091256 - 18 Sep 2021

Cited by 14 | Viewed by 3430

Abstract

Nonalcoholic fatty liver disease (NAFLD) refers to the pathologic buildup of extra fat in the form of triglycerides in liver cells without excessive alcohol intake. NAFLD became the most common cause of chronic liver disease that is tightly associated with key aspects of metabolic disorders, including insulin resistance, obesity, diabetes, and metabolic syndrome. It is generally accepted that multiple mechanisms and pathways are involved in the pathogenesis of NAFLD. Heredity, sedentary lifestyle, westernized high sugar saturated fat diet, metabolic derangements, and gut microbiota, all may interact on a on genetically susceptible individual to cause the disease initiation and progression. While there is an unquestionable role for gene-diet interaction in the etiopathogenesis of NAFLD, it is increasingly apparent that epigenetic processes can orchestrate many aspects of this interaction and provide additional mechanistic insight. Exciting research demonstrated that epigenetic alterations in chromatin can influence gene expression chiefly at the transcriptional level in response to unbalanced diet, and therefore predispose an individual to NAFLD. Thus, further discoveries into molecular epigenetic mechanisms underlying the link between nutrition and aberrant hepatic gene expression can yield new insights into the pathogenesis of NAFLD, and allow innovative epigenetic-based strategies for its early prevention and targeted therapies. Herein, we outline the current knowledge of the interactive role of a high-fat high-calories diet and gene expression through DNA methylation and histone modifications on the pathogenesis of NAFLD. We also provide perspectives on the advancement of the epigenomics in the field and possible shortcomings and limitations ahead. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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11 pages, 967 KiB

Open AccessReview

Role of Epigenetics in Type 2 Diabetes and Obesity

by Rosanna Capparelli and Domenico Iannelli

Biomedicines 2021, 9(8), 977; https://doi.org/10.3390/biomedicines9080977 - 08 Aug 2021

Cited by 7 | Viewed by 3828

Abstract

Epigenetic marks the genome by DNA methylation, histone modification or non-coding RNAs. Epigenetic marks instruct cells to respond reversibly to environmental cues and keep the specific gene expression stable throughout life. In this review, we concentrate on DNA methylation, the mechanism often associated with transgenerational persistence and for this reason frequently used in the clinic. A large study that included data from 10,000 blood samples detected 187 methylated sites associated with body mass index (BMI). The same study demonstrates that altered methylation results from obesity (OB). In another study the combined genetic and epigenetic analysis allowed us to understand the mechanism associating hepatic insulin resistance and non-alcoholic disease in Type 2 Diabetes (T2D) patients. The study underlines the therapeutic potential of epigenetic studies. We also account for seemingly contradictory results associated with epigenetics. Full article

(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)

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