Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic in countries that consume a Western diet, and it can lead to irreversible cirrhosis and hepatocellular carcinoma
Exposure to endocrine-disrupting chemicals (EDCs) in early life could represent a 'new' risk factor for the development of NAFLD later in life
The mechanism of action of EDCs involves both the modulation of nuclear hormone receptor function via co-regulator proteins and the alteration of the epigenome (that is, DNA methylation and histone modification)
Animal model studies suggest causality between early-life exposure to certain EDCs and NAFLD presentation later in life
Studies are needed to define whether there is a causal relationship between EDC exposure and development of NAFLD in humans, as well as to develop new prevention and treatment regimes
A growing epidemic of nonalcoholic fatty liver disease (NAFLD) is paralleling the increase in the incidence of obesity and diabetes mellitus in countries that consume a Western diet. As NAFLD can lead to life-threatening conditions such as cirrhosis and hepatocellular carcinoma, an understanding of the factors that trigger its development and pathological progression is needed. Although by definition this disease is not associated with alcohol consumption, exposure to environmental agents that have been linked to other diseases might have a role in the development of NAFLD. Here, we focus on one class of these agents, endocrine-disrupting chemicals (EDCs), and their potential to influence the initiation and progression of a cascade of pathological conditions associated with hepatic steatosis (fatty liver). Experimental studies have revealed several potential mechanisms by which EDC exposure might contribute to disease pathogenesis, including the modulation of nuclear hormone receptor function and the alteration of the epigenome. However, many questions remain to be addressed about the causal link between acute and chronic EDC exposure and the development of NAFLD in humans. Future studies that address these questions hold promise not only for understanding the linkage between EDC exposure and liver disease but also for elucidating the molecular mechanisms that underpin NAFLD, which in turn could facilitate the development of new prevention and treatment opportunities.
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The authors acknowledge K. Phillips, M. Feingold and D. Moore for helpful discussions on nonalcoholic fatty liver disease, and the National Institute of Environmental Health Sciences for support (grants 1R01ES023206, P30ES023512 and U01ES026719 to C.L.W.).
The authors declare no competing financial interests.
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Foulds, C., Treviño, L., York, B. et al. Endocrine-disrupting chemicals and fatty liver disease. Nat Rev Endocrinol 13, 445–457 (2017). https://doi.org/10.1038/nrendo.2017.42
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