Epigenetic Mechanisms of Endocrine-Disrupting Chemicals in Obesity

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.

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Epigenetic modifications associated with in utero exposure to endocrine disrupting chemicals BPA, DDT and Pb

Reviews on Environmental Health ◽

10.1515/reveh-2018-0059 ◽

2019 ◽

Vol 34 (4) ◽

pp. 309-325 ◽

Cited By ~ 6

Author(s):

Chinonye Doris Onuzulu ◽

Oluwakemi Anuoluwapo Rotimi ◽

Solomon Oladapo Rotimi

Keyword(s):

Endocrine Disruptors ◽

Endocrine Disrupting Chemicals ◽

Endocrine System ◽

Environmental Chemicals ◽

Epigenetic Mechanisms ◽

Epigenetic Alterations ◽

Endocrine Disrupting ◽

Non Coding Rnas ◽

Hormone System ◽

Developmental Windows

Abstract Endocrine disrupting chemicals (EDCs) are xenobiotics which adversely modify the hormone system. The endocrine system is most vulnerable to assaults by endocrine disruptors during the prenatal and early development window, and effects may persist into adulthood and across generations. The prenatal stage is a period of vulnerability to environmental chemicals because the epigenome is usually reprogrammed during this period. Bisphenol A (BPA), lead (Pb), and dichlorodiphenyltrichloroethane (DDT) were chosen for critical review because they have become serious public health concerns globally, especially in Africa where they are widely used without any regulation. In this review, we introduce EDCs and describe the various modes of action of EDCs and the importance of the prenatal and developmental windows to EDC exposure. We give a brief overview of epigenetics and describe the various epigenetic mechanisms: DNA methylation, histone modifications and non-coding RNAs, and how each of them affects gene expression. We then summarize findings from previous studies on the effects of prenatal exposure to the endocrine disruptors BPA, Pb and DDT on each of the previously described epigenetic mechanisms. We also discuss how the epigenetic alterations caused by these EDCs may be related to disease processes.

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Concentrations of endocrine disrupting chemicals in liver and adipose tissue in United Kingdom

Endocrine Abstracts ◽

10.1530/endoabs.44.p182 ◽

2016 ◽

Author(s):

Thozhukat Sathyapalan ◽

Lesa Aylward ◽

Martin Rose ◽

Steve Petch ◽

Natalie Thatcher ◽

...

Keyword(s):

Adipose Tissue ◽

United Kingdom ◽

Endocrine Disrupting Chemicals ◽

Endocrine Disrupting

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Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin

Clinical Chemistry ◽

10.1373/clinchem.2004.032482 ◽

2004 ◽

Vol 50 (9) ◽

pp. 1511-1525 ◽

Cited By ~ 602

Author(s):

Ursula Meier ◽

Axel M Gressner

Keyword(s):

Adipose Tissue ◽

Energy Metabolism ◽

Energy Homeostasis ◽

Clinical Chemistry ◽

The Body ◽

Storage Site ◽

Endocrine Regulation ◽

Highly Active ◽

Glucose And Lipid Metabolism ◽

Organ Systems

Abstract Background: Recent studies point to the adipose tissue as a highly active endocrine organ secreting a range of hormones. Leptin, ghrelin, adiponectin, and resistin are considered to take part in the regulation of energy metabolism. Approach: This review summarizes recent knowledge on leptin and its receptor and on ghrelin, adiponectin, and resistin, and emphasizes their roles in pathobiochemistry and clinical chemistry. Content: Leptin, adiponectin, and resistin are produced by the adipose tissue. The protein leptin, a satiety hormone, regulates appetite and energy balance of the body. Adiponectin could suppress the development of atherosclerosis and liver fibrosis and might play a role as an antiinflammatory hormone. Increased resistin concentrations might cause insulin resistance and thus could link obesity with type II diabetes. Ghrelin is produced in the stomach. In addition to its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. These hormones have important roles in energy homeostasis, glucose and lipid metabolism, reproduction, cardiovascular function, and immunity. They directly influence other organ systems, including the brain, liver, and skeletal muscle, and are significantly regulated by nutritional status. This newly discovered secretory function has extended the biological relevance of adipose tissue, which is no longer considered as only an energy storage site. Summary: The functional roles, structures, synthesis, analytical aspects, and clinical significance of leptin, ghrelin, adiponectin, and resistin are summarized.

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Environmental Obesogens: Mechanisms and Controversies

The Annual Review of Pharmacology and Toxicology ◽

10.1146/annurev-pharmtox-010818-021304 ◽

2019 ◽

Vol 59 (1) ◽

pp. 89-106 ◽

Cited By ~ 50

Author(s):

Jerrold J. Heindel ◽

Bruce Blumberg

Keyword(s):

Hormonal Regulation ◽

Food Packaging ◽

Endocrine Disrupting Chemicals ◽

Caloric Intake ◽

Environmental Chemicals ◽

Endocrine Regulation ◽

Complete Understanding ◽

Endocrine Disrupting ◽

Care Costs

Obesity is a worldwide pandemic in adults as well as children and adds greatly to health care costs through its association with type 2 diabetes, metabolic syndrome, cardiovascular disease, and cancers. The prevailing medical view of obesity is that it results from a simple imbalance between caloric intake and energy expenditure. However, numerous other factors are important in the etiology of obesity. The obesogen hypothesis proposes that environmental chemicals termed obesogens promote obesity by acting to increase adipocyte commitment, differentiation, and size by altering metabolic set points or altering the hormonal regulation of appetite and satiety. Many obesogens are endocrine disrupting chemicals that interfere with normal endocrine regulation. Endocrine disrupting obesogens are abundant in our environment, used in everyday products from food packaging to fungicides. In this review, we explore the evidence supporting the obesogen hypothesis, as well as the gaps in our knowledge that are currently preventing a complete understanding of the extent to which obesogens contribute to the obesity pandemic.

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Chronic exposure of mice to environmental endocrine-disrupting chemicals disturbs their energy metabolism

Toxicology Letters ◽

10.1016/j.toxlet.2014.01.006 ◽

2014 ◽

Vol 225 (3) ◽

pp. 392-400 ◽

Cited By ~ 35

Author(s):

Yuanxiang Jin ◽

Xiaojian Lin ◽

Wenyu Miao ◽

Tao Wu ◽

Hangjie Shen ◽

...

Keyword(s):

Energy Metabolism ◽

Chronic Exposure ◽

Endocrine Disrupting Chemicals ◽

Endocrine Disrupting

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Endocrine-disrupting chemicals—Mechanisms of action on male reproductive system

Toxicology and Industrial Health ◽

10.1177/0748233717695160 ◽

2017 ◽

Vol 33 (7) ◽

pp. 601-609 ◽

Cited By ~ 37

Author(s):

Iwona Sidorkiewicz ◽

Kamil Zaręba ◽

Sławomir Wołczyński ◽

Jan Czerniecki

Keyword(s):

Reproductive System ◽

Meta Analysis ◽

Endocrine Disrupting Chemicals ◽

Endocrine System ◽

Reproductive Function ◽

Male Reproductive System ◽

Future Research ◽

Male Reproductive Function ◽

Endocrine Disrupting ◽

Exogenous Compounds

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that can cause disturbances in the endocrine system and have multiple harmful effects on health by targeting different organs and systems in the human body. Mass industrial production and widespread use of EDCs have resulted in worldwide contamination. Accumulating evidence suggest that human exposure to EDCs is related to the impairment of male reproductive function and can interrupt other hormonally regulated metabolic processes, particularly if exposure occurs during early development. Investigation of studies absent in previous reviews and meta-analysis of adverse effects of EDCs on functioning of the male reproductive system is the core of this work. Four main modes of action of EDCs on male fertility have been summarized in this review. First, studies describing estrogen- pathway disturbing chemicals are investigated. Second, androgen-signaling pathway alterations and influence on androgen sensitive tissues are examined. Third, evaluation of steroidogenesis dysfunction is discussed by focusing on the steroid hormone biosynthesis pathway, which is targeted by EDCs. Last, the reportedly destructive role of reactive oxygen species (ROS) on sperm function is discussed. Spermatogenesis is a remarkably complex process, hence multiple studies point out various dysfunctions depending on the development state at which the exposure occurred. Collected data show the need to account for critical windows of exposure such as fetal, perinatal and pubertal periods as well as effects of mixtures of several compounds in future research.

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New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17217787 ◽

2020 ◽

Vol 17 (21) ◽

pp. 7787

Author(s):

Letizia Pitto ◽

Francesca Gorini ◽

Fabrizio Bianchi ◽

Elena Guzzolino

Keyword(s):

Methylation Status ◽

Endocrine Disrupting Chemicals ◽

Epidemiological Studies ◽

Thyroid Diseases ◽

Epigenetic Alterations ◽

Chemical Action ◽

Endocrine Disrupting ◽

Fetal Thyroid

In recent years, the presence in the environment of chemical compounds with thyroid-disrupting effects is progressively increased. This phenomenon has risen concern for human health as the preservation of thyroid system homeostasis is essential for fetal development and for maintaining psychological and physiological wellbeing. An increasing number of studies explored the role of different classes of toxicants in the occurrence and severity of thyroid diseases, but large epidemiological studies are limited and only a few animal or in vitro studies have attempted to identify the mechanisms of chemical action. Recently, epigenetic changes such as alteration of methylation status or modification of non-coding RNAs have been suggested as correlated to possible deleterious effects leading to different thyroid disorders in susceptible individuals. This review aims to analyze the epigenetic alterations putatively induced by chemical exposures and involved in the onset of frequent thyroid diseases such as thyroid cancer, autoimmune thyroiditis and disruption of fetal thyroid homeostasis.

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Environmental Contamination and Human Exposure to Select Endocrine-Disrupting Chemicals: A Review

Sustainable Chemistry ◽

10.3390/suschem2020020 ◽

2021 ◽

Vol 2 (2) ◽

pp. 343-380

Author(s):

Seethappan Sangeetha ◽

Krishnamoorthi Vimalkumar ◽

Bommanna G. Loganathan

Keyword(s):

Environmental Contamination ◽

Human Exposure ◽

Endocrine Disrupting Chemicals ◽

Endocrine Disrupting Compounds ◽

Indoor Dust ◽

Future Research ◽

Environmental Matrices ◽

Aquatic Contamination ◽

Endocrine Disrupting ◽

Exogenous Compounds

Endocrine-disrupting compounds (EDCs) are exogenous compounds that interfere with the normal hormone functions and ultimately lead to health disorders. Parabens, phenols, and phthalates are well-known EDCs, produced globally in large quantities and widely used in a variety of applications. Several studies have monitored these compounds in a variety of environmental matrices, including air, water, sediment, fish, human tissues, soil, indoor dust, and biosolids, etc. In recent years, environmental contamination and human exposure to these chemicals have become a great concern, due to their residue levels exceeding the permissible/acceptable limits. In this review, we focus on the origin of these EDCs, aquatic contamination pathways, distribution, human exposure, health implications, and healthcare costs. Further, this review identifies critical challenges and future research needs in removing or minimizing environmental contamination and exposure to these chemicals to protect living resources.

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Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter?

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17249403 ◽

2020 ◽

Vol 17 (24) ◽

pp. 9403

Author(s):

Brigitte Le Magueresse-Battistoni

Keyword(s):

Adipose Tissue ◽

Metabolic Diseases ◽

Endocrine Disrupting Chemicals ◽

Environmental Chemicals ◽

Metabolic Disturbances ◽

Adipose Tissue Dysfunction ◽

Realistic Option ◽

Endocrine Disrupting ◽

Public Health Challenges ◽

Males And Females

Obesity and metabolic-related diseases, among which diabetes, are prominent public health challenges of the 21st century. It is now well acknowledged that pollutants are a part of the equation, especially endocrine-disrupting chemicals (EDCs) that interfere with the hormonal aspect. The aim of the review is to focus on adipose tissue, a central regulator of energy balance and metabolic homeostasis, and to highlight the significant differences in the endocrine and metabolic aspects of adipose tissue between males and females which likely underlie the differences of the response to exposure to EDCs between the sexes. Moreover, the study also presents an overview of several mechanisms of action by which pollutants could cause adipose tissue dysfunction. Indeed, a better understanding of the mechanism by which environmental chemicals target adipose tissue and cause metabolic disturbances, and how these mechanisms interact and sex specificities are essential for developing mitigating and sex-specific strategies against metabolic diseases of chemical origin. In particular, considering that a scenario without pollutant exposure is not a realistic option in our current societies, attenuating the deleterious effects of exposure to pollutants by acting on the gut-adipose tissue axis may constitute a new direction of research.

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