Review

. 2019 Sep;6(3):80-94.

doi: 10.1007/s40572-019-00232-w.

Mechanisms of Environmental Contributions to Fatty Liver Disease

Banrida Wahlang^{1

2}, Jian Jin³, Juliane I Beier^{4

5}, Josiah E Hardesty¹, Erica F Daly³, Regina D Schnegelberger⁶, K Cameron Falkner¹, Russell A Prough⁷, Irina A Kirpich^{1

8

9}, Matthew C Cave^{10

11

12

13

14

15

16

17

18}

Affiliations

¹ Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
² University of Louisville Superfund Research Center, University of Louisville, Louisville, KY, 40202, USA.
³ Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
⁴ Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁵ Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁶ Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁷ Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
⁸ Hepatobiology & Toxicology COBRE Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
⁹ University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY, 40202, USA.
¹⁰ Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹¹ University of Louisville Superfund Research Center, University of Louisville, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹² Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹³ Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹⁴ Hepatobiology & Toxicology COBRE Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹⁵ University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹⁶ The Robley Rex Veterans Affairs Medical Center, Louisville, KY, 40206, USA. matt.cave@louisville.edu.
¹⁷ The Jewish Hospital Liver Transplant Program, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹⁸ Kosair Charities Clinical & Translational Research Building, 505 South Hancock Street, Louisville, KY, 40202, USA. matt.cave@louisville.edu.

PMID: 31134516
PMCID: PMC6698418
DOI: 10.1007/s40572-019-00232-w

Review

Mechanisms of Environmental Contributions to Fatty Liver Disease

Banrida Wahlang et al. Curr Environ Health Rep. 2019 Sep.

. 2019 Sep;6(3):80-94.

doi: 10.1007/s40572-019-00232-w.

Authors

Affiliations

¹ Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
² University of Louisville Superfund Research Center, University of Louisville, Louisville, KY, 40202, USA.
³ Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
⁴ Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁵ Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁶ Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁷ Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
⁸ Hepatobiology & Toxicology COBRE Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
⁹ University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY, 40202, USA.
¹⁰ Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹¹ University of Louisville Superfund Research Center, University of Louisville, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹² Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹³ Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹⁴ Hepatobiology & Toxicology COBRE Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹⁵ University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹⁶ The Robley Rex Veterans Affairs Medical Center, Louisville, KY, 40206, USA. matt.cave@louisville.edu.
¹⁷ The Jewish Hospital Liver Transplant Program, Louisville, KY, 40202, USA. matt.cave@louisville.edu.
¹⁸ Kosair Charities Clinical & Translational Research Building, 505 South Hancock Street, Louisville, KY, 40202, USA. matt.cave@louisville.edu.

PMID: 31134516
PMCID: PMC6698418
DOI: 10.1007/s40572-019-00232-w

Abstract

Purpose: Fatty liver disease (FLD) affects over 25% of the global population and may lead to liver-related mortality due to cirrhosis and liver cancer. FLD caused by occupational and environmental chemical exposures is termed "toxicant-associated steatohepatitis" (TASH). The current review addresses the scientific progress made in the mechanistic understanding of TASH since its initial description in 2010.

Recent findings: Recently discovered modes of actions for volatile organic compounds and persistent organic pollutants include the following: (i) the endocrine-, metabolism-, and signaling-disrupting chemical hypotheses; (ii) chemical-nutrient interactions and the "two-hit" hypothesis. These key hypotheses were then reviewed in the context of the steatosis adverse outcome pathway (AOP) proposed by the US Environmental Protection Agency. The conceptual understanding of the contribution of environmental exposures to FLD has progressed significantly. However, because this is a new research area, more studies including mechanistic human data are required to address current knowledge gaps.

Keywords: Endocrine disruption; Polychlorinated biphenyls; Signaling disruption; TASH; Toxicant-associated steatohepatitis; Vinyl chloride.

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Conflict of interest statement

CONFLICT OF INTEREST

Banrida Wahlang, Jian Jin, Juliane I. Beier, Josiah E. Hardesty, Erica F. Daly, Regina D. Schnegelberger, K. Cameron Falkner, Russell A. Prough, Irina A Kirpich, and Matthew C. Cave each declare no potential conflicts of interest.

Figures

**Figure 1.. Selected Modes of Action for Volatile Organic Compounds and Persistent Organic Pollutants in Fatty Liver Disease.**
These modes of action are related to the endocrine, metabolism, and signaling disrupting hypotheses as well as nutritional interactions and the two ‘hit’ hypothesis.

See this image and copyright information in PMC

Cited by

Effect of Epidermal Growth Factor Treatment and Polychlorinated Biphenyl Exposure in a Dietary-Exposure Mouse Model of Steatohepatitis.
Hardesty JE, Wahlang B, Prough RA, Head KZ, Wilkey D, Merchant M, Shi H, Jin J, Cave MC. Hardesty JE, et al. Environ Health Perspect. 2021 Mar;129(3):37010. doi: 10.1289/EHP8222. Epub 2021 Mar 31. Environ Health Perspect. 2021. PMID: 33788613 Free PMC article.
Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.
Klinge CM, Piell KM, Petri BJ, He L, Zhang X, Pan J, Rai SN, Andreeva K, Rouchka EC, Wahlang B, Beier JI, Cave MC. Klinge CM, et al. Environ Epigenet. 2021 Sep 17;7(1):dvab008. doi: 10.1093/eep/dvab008. eCollection 2021. Environ Epigenet. 2021. PMID: 34548932 Free PMC article.
Blood BTEXS and heavy metal levels are associated with liver injury and systemic inflammation in Gulf states residents.
Werder EJ, Beier JI, Sandler DP, Falkner KC, Gripshover T, Wahlang B, Engel LS, Cave MC. Werder EJ, et al. Food Chem Toxicol. 2020 May;139:111242. doi: 10.1016/j.fct.2020.111242. Epub 2020 Mar 20. Food Chem Toxicol. 2020. PMID: 32205228 Free PMC article.
Environment-wide association study of elevated liver enzymes: results from the Korean National Environmental Health Survey 2018-2022.
Chi Y, Park JT, Na S, Kwak K. Chi Y, et al. Ann Occup Environ Med. 2023 Jul 31;35:e27. doi: 10.35371/aoem.2023.35.e27. eCollection 2023. Ann Occup Environ Med. 2023. PMID: 37701484 Free PMC article.
Associations Between Residential Exposure to Volatile Organic Compounds and Liver Injury Markers.
Wahlang B, Gripshover TC, Gao H, Krivokhizhina T, Keith RJ, Sithu ID, Rai SN, Bhatnagar A, McClain CJ, Srivastava S, Cave MC. Wahlang B, et al. Toxicol Sci. 2021 Dec 28;185(1):50-63. doi: 10.1093/toxsci/kfab119. Toxicol Sci. 2021. PMID: 34668566 Free PMC article.

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Mechanisms of Environmental Contributions to Fatty Liver Disease

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