Mechanisms of Environmental Contributions to Fatty Liver Disease

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.

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.