Endocrine Disruptors and Developmental Origins of Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic worldwide, particularly in countries that consume a Western diet, and can lead to life-threatening conditions such as cirrhosis and hepatocellular carcinoma. With increasing prevalence of NAFLD in both children and adults, an understanding of the factors that promote NAFLD development and progression is crucial. Environmental agents, including endocrine-disrupting chemicals (EDCs), which have been linked to other diseases, may play a role in NAFLD development. Increasing evidence supports a developmental origin of liver disease, and early-life exposure to EDCs could represent one risk factor for the development of NAFLD later in life. Rodent studies provide the strongest evidence for this link, but further studies are needed to define whether there is a causal link between early-life EDC exposure and NAFLD development in humans. Elucidating the molecular mechanisms underlying development of NAFLD in the context of developmental EDC exposures may identify biomarkers for people at risk, as well as potential intervention and/or therapeutic opportunities for the disease.

Figure 1.

Developmental exposure to endocrine-disrupting chemicals and the development of NAFLD in adulthood. Rodent studies have shown that early-life exposure to BPA, TBT, B[a]P, PFOS, PFOA, DEHP, and As is associated with hepatic steatosis, hepatic inflammation (one aspect of NASH), and/or HCC. As, arsenic; B[a]P, benzo[a]pyrene; BPA, bisphenol A; DEHP, bis(2-ethylhexyl) phthalate; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; TBT, terbutyltin.