Purpose of Review
Non-alcoholic fatty liver disease (NAFLD) is the most prominent chronic liver disease in Western countries, affecting approximately 25% of the population worldwide. Sex-specific differences in the development of NAFLD are apparent. While obesity and insulin resistance are major contributors to the increasing prevalence of NAFLD, a growing body of literature suggests that exposure to persistent endocrine-disrupting chemicals (pEDCs) may also play a role. This review summarizes recent (2011 and later) scientific literature investigating exposures to pEDCs, specifically persistent organic pollutants (POPs), and NAFLD, with a focus on sex-specific associations.
The overwhelming majority of studies were conducted in single-sex animal models and provide biological evidence that exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin polychlorinated biphenyls, and other POPs or POP mixtures are negatively associated with liver health. There were four cross-sectional epidemiological studies in humans that reported associations for several POPs, including polychlorinated biphenyls and perfluorinated chemicals, with elevated liver enzymes. Only one of these studies, using a sample of gastric bypass surgery patients, examined sex-specific associations of POPs and liver enzymes, finding adverse associations among women only. The noticeable lack of studies investigating how differences (i.e., biochemical, physiological, and behavioral) between men and women may influence associations of pEDCs and NAFLD represents a large research gap in environmental health. Sexual dimorphism in metabolic processes throughout the body, including the liver, is established but often overlooked in the designs and analyses of studies. Other factors identified in this review that may also act to modulate associations of environmental chemicals and NAFLD are reproductive status and dietary nutrient intakes, which also remain understudied in the literature.
Despite knowledge of sexual dimorphism in the actions of pEDCs, as well as in metabolic processes related to NAFLD development, few experimental or epidemiological studies have investigated sex-dependent associations. Future studies, especially those in humans, should be designed to address this research need. Consideration of other factors, such as reproductive status, dietary intakes, and mixtures of chemicals with varying endocrine-disrupting capabilities, should be explored.
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Aryl hydrocarbon receptor
Brominated diphenyl ethers
Persistent endocrine-disrupting chemical
Gamma glutamyl transferase
Non-alcoholic fatty liver disease
National Health and Nutrition Examination Surveys
Persistent organic chemicals
Papers of particular interest, published recently, have been highlighted as: • Of importance
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Andrea L. Deierlein is supported by the following grant: NIEHS R00 ES023474-03.
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Synthetic Chemicals and Health
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Deierlein, A.L., Rock, S. & Park, S. Persistent Endocrine-Disrupting Chemicals and Fatty Liver Disease. Curr Envir Health Rpt 4, 439–449 (2017). https://doi.org/10.1007/s40572-017-0166-8